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Thousands struggle with acute and chronic intestinal injury due to various causes. Epithelial intestinal healing is dependent on phenotypic transitions to a mobile phenotype. Focal adhesion kinase (FAK) is a ubiquitous protein that is essential for cell mobility. This phenotype change is mediated by FAK activation and proves to be a promising target for pharmaceutical intervention. While FAK is crucial for intestinal healing, new evidence connects FAK with innate immunity and the importance it plays in macrophage/monocyte chemotaxis, as well as other intracellular signaling cascades. These cascades play a part in macrophage/monocyte polarization, maturation, and inflammation that is associated with intestinal injury. Colony stimulating factors (CSFs) such as macrophage colony stimulating factor (M-CSF/CSF-1) and granulocyte macrophage colony stimulating factor (GM-CSF/CSF-2) play a critical role in maintaining homeostasis within intestinal mucosa by crosstalk capabilities between macrophages and epithelial cells. The communication between these cells is imperative in orchestrating healing upon injury. Diving deeper into these connections may allow us a greater insight into the role that our immune system plays in healing, as well as a better comprehension of inflammatory diseases of the gut. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process composed of different stages, which involves extensive communication between the different cellular factors of the extracellular matrix (ECM). The radio frequency electromagnetic field (RF-EMF) has been used to accelerate the wound-healing process and it has been found to enhance cell alignment and mobility. The conventional methods for cell mobility analysis in an electromagnetic field generated by a radiation source are not advisable due to the low-precision, nonuniform distribution of the field, low efficiency of the analysis in batch and the lack of system integration for autonomous on-body operation. Here, a novel and versatile electromagnetic exposure system integrated with a microfluidic chip was fabricated to explore the EMF-induced response. A gradient electromagnetic field in a two-dimensional plane has been successfully established in the microchambers placed along the field line. In this work, by deploying our radiation experiments in vitro, we validated the on-chip monitoring of cell response to exposure. This electromagnetic field was simulated and human amniotic epithelial cells (HAECs) were cultured in different microchambers for continuous exposure to the electromagnetic field excited by a monopole RF antenna (1.8 GHz). New protrusions were generated and an obvious increase in filopodia with the increased field intensity was investigated. Meanwhile, the variation in intracellular Ca2+ concentration under the electromagnetic field was examined. The inhibitory effect of the Ca2+ circulation was further inspected to reveal the potential downstream signaling pathway in the RF-EMF-related bioassay, suggesting that cytoskeletal dynamics of cells under exposure are highly associated with the EGF receptor (EGFR)-cytoskeleton downstream signaling pathway. Finally, the field-induced cell elongation and alignment parallel to the field direction were observed. Additionally, the subsequent recovery (field withdrawal) and re-establishment (field re-exposure) were explored. These results indicated that this reliable and versatile exposure system for bioassay could achieve precise and high-throughput detection of the RF-EMF-induced cytoskeletal reorganization in vitro and evaluate the possible health risk from RF-EMF exposure. [ABSTRACT FROM AUTHOR]

Oxidative damage has been implicated in the pathogenesis of numerous disorders by affecting the normal functions of several tissues. Further, oxidative stress acts within cells to influence cell morphology and the behavior of cell migration. The movement and migration of cells are crucial during the development of organisms as they transition from embryo to adult, and for the homeostasis of adult tissues. Epicatechin (EC) is a natural flavonoid derived mostly from tea, chocolate, and red wine. We investigated the protective impact of EC on D‐galactose(D‐gal)/rotenone‐injured NIH3T3 cells and found alterations in cell dynamics throughout the procedure. The results reveal that D‐gal/rotenone stimulation can cause the cell area to expand and the number of cellular protrusions to increase. EC intervention can considerably minimize the oxidative damage of rotenone on NIH3T3 cells (p < 0.05) but showed little influence on cell damage induced by D‐gal. Furthermore, the corrective ability of EC as an antioxidant is reflected in a dose‐dependent effect on cell movement, including variations in movement speed and distance. Overall, from the perspective of cell morphology and cell motility, EC has a good protective impact on cells harmed by rotenone induced oxidative damage, as well as corrective properties as an antioxidant to balance intracellular oxidative stress, which allowing for a more comprehensive evaluation of antioxidant performance of EC. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM), which is a malignant primary brain tumor, is the cancer that spreads most aggressively into the adjacent brain tissue. Patients with metastatic GBM have a poor chance of survival. In this study, we examined the anti-GBM mobility effect of small protein, called GMI, which is cloned and purified from Ganoderma microsporum. Proteomic profiles showed that GMI-mediated proteins were involved in cell motility and cell growth functions. Specifically, we demonstrated that GMI significantly suppressed cell migration and invasion of GBM cells. GMI combined with temozolomide (TMZ), which is a traditional chemotherapeutic agent for GBM treatment, synergistically inhibited motility in GBM cells. Mechanistically, we demonstrated that GMI induced proteasome-dependent degradation of Slug, which is a critical transcription factor, is frequently linked to metastasis and drug resistance in GBM. Knockdown of Slug reduced cell viability and colony formation of GBM cells but enhanced TMZ-suppressed cell migration and viability. The results of this study show that targeting Slug degradation is involved in GMI-suppressed mobility of GBM cells. Moreover, GMI may be a potential supplementary agent for the suppression of GBM. • GMI inhibits cell migration and invasion of GBM cells. • GMI synergistically enhances cytotoxic effect of temozolomide. • GMI induces proteasome-dependent Slug degradation. • Knockdown of Slug inhibits cell viability and migration of GBM cells. • Slug involves in temozolomide resistant pathway. [ABSTRACT FROM AUTHOR]

Gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) are frequently used biomaterials for 3D bioprinting, with individual well-established material characteristics. To identify an ideal combination of GelMA and HAMA for chondrogenesis, a novel, primary human chondrocyte COL2A1-Gaussia luciferase reporter system (HuCol2gLuc) was developed. With this non-destructive, high-throughput temporal assay, Gaussia luciferase is secreted from the cells and used as a proxy for measuring type II collagen production. GelMA:HAMA ratios were screened using the reporter system before proceeding to 3D bioprinting. This method is efficient, saving on time and materials, resulting in a streamlined process of biomaterial optimization. The screen revealed that the addition of HAMA to GelMA improved chondrogenesis over GelMA (15%) alone. Storage moduli were measured using dynamic mechanical analysis of the same GelMA:HAMA ratios and established an initial threshold for chondrogenesis of ∼30kPa. To determine if biomaterial storage moduli impact cell mobility, human primary chondrocytes transduced with green fluorescent protein (GFP) were 3D bioprinted in either 1:1 or 2:1 ratios with storage moduli of 32kPa and 57.9kPa, respectively. We found that reduced cell mobility, in the stiffer biomaterial, had higher type II collagen expression, than the softer material with more cell mobility. Finally, after 3D bioprinting with HuCol2gLuc cells we successfully identified an optimal combination (2:1) of GelMA:HAMA and photo-crosslinking time (38s) for chondrogenesis. One challenge of 3D bioprinting is identifying ideal biomaterials that stimulate articular cartilage development. To identify an optimal combination of gelatin methacrylate and hyaluronic acid methacrylate for chondrogenesis we developed a primary human chondrocyte type II collagen Gaussia luciferase reporter cell (HuCol2gLuc). This non-destructive, high-throughput assay uses a secreted Gaussia luciferase as a proxy for temporal type II collagen production. This reporter system streamlines the biomaterial optimization process before 3D bioprinting. We also used it to determine the level of stiffness required for chondrogenesis. And for the first time, we quantified chondrocyte mobility in a 3D bioprinted construct. Together these results indicate that a biomaterial with a higher storage modulus and less cell mobility, improves chondrogenesis. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatoblastoma (HBL) is a rare hepatic malignancy occurring mainly in early childhood. Although recently developed treatment regimens have improved prognosis, many refractory cases still exist, and the anticancer drug cis-diamminedichloroplatinum—cisplatin—primarily used in HBL treatment often induces severe side effects. Therefore, more effective and safer therapies are needed. In this study, we demonstrate that the expression level of ADAM32 is particularly high in HBL tissue samples and is associated with poor prognosis in various cancer types through the regulation of cancer cell proliferation, stemness, migration, invasion, and acquired resistance to chemotherapy. Our results thus indicate that ADAM32 could be a promising candidate therapeutic target molecule, and provide new insights into the molecular mechanisms of HBL carcinogenesis. Outcomes of pediatric hepatoblastoma (HBL) have improved, but refractory cases still occur. More effective and safer drugs are needed that are based on molecular mechanisms. A disintegrin and metalloproteases (ADAMs) are expressed with high frequency in various human carcinomas and play an important role in cancer progression. In this study, we analyzed expression of ADAMs in HBL with a cDNA microarray dataset and found that the expression level of ADAM32 is particularly high. To investigate the role of ADAM32 in cancer, forced expression or knockdown experiments were conducted with HepG2 and HBL primary cells. Colony formation, cell migration and invasion, and cell viability were increased in HepG2 expressing ADAM32, whereas knockdown of ADAM32 induced a decrease in these cellular functions. Quantitative RT-PCR demonstrated an association between ADAM32 expression and the expression of genes related to cancer stem cells and epithelial–mesenchymal transition (EMT), suggesting a role of ADAM32 in cancer stemness and EMT. Furthermore, knockdown of ADAM32 increased cisplatin-induced apoptosis, and this effect was attenuated by a caspase-8 inhibitor, suggesting that ADAM32 plays a role in extrinsic apoptosis signaling. We conclude that ADAM32 plays a crucial role in progression of HBL, so it might be a promising molecular target in anticancer therapy. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process composed of different stages, which involves extensive communication between the different cellular factors of the extracellular matrix (ECM). The radio frequency electromagnetic field (RF-EMF) has been used to accelerate the wound-healing process and it has been found to enhance cell alignment and mobility. The conventional methods for cell mobility analysis in an electromagnetic field generated by a radiation source are not advisable due to the low-precision, nonuniform distribution of the field, low efficiency of the analysis in batch and the lack of system integration for autonomous on-body operation. Here, a novel and versatile electromagnetic exposure system integrated with a microfluidic chip was fabricated to explore the EMF-induced response. A gradient electromagnetic field in a two-dimensional plane has been successfully established in the microchambers placed along the field line. In this work, by deploying our radiation experiments in vitro, we validated the on-chip monitoring of cell response to exposure. This electromagnetic field was simulated and human amniotic epithelial cells (HAECs) were cultured in different microchambers for continuous exposure to the electromagnetic field excited by a monopole RF antenna (1.8 GHz). New protrusions were generated and an obvious increase in filopodia with the increased field intensity was investigated. Meanwhile, the variation in intracellular Ca2+ concentration under the electromagnetic field was examined. The inhibitory effect of the Ca2+ circulation was further inspected to reveal the potential downstream signaling pathway in the RF-EMF-related bioassay, suggesting that cytoskeletal dynamics of cells under exposure are highly associated with the EGF receptor (EGFR)-cytoskeleton downstream signaling pathway. Finally, the field-induced cell elongation and alignment parallel to the field direction were observed. Additionally, the subsequent recovery (field withdrawal) and re-establishment (field re-exposure) were explored. These results indicated that this reliable and versatile exposure system for bioassay could achieve precise and high-throughput detection of the RF-EMF-induced cytoskeletal reorganization in vitro and evaluate the possible health risk from RF-EMF exposure.

Aggressive invasiveness is a common feature of malignant gliomas, despite their high level of tumor heterogeneity and possible diverse cell origins. Therefore, it is important to explore new therapeutic methods. In this study, we evaluated and compared the effects of graphene (GN) and reduced graphene oxides (rGOs) on a highly invasive and neoplastic cell line, U87. The surface functional groups of the GN and rGO flakes were characterized by X-ray photoelectron spectroscopy. The antitumor activity of these flakes was obtained by using the neutral red assay and their anti-migratory activity was determined using the wound healing assay. Further, we investigated the mRNA and protein expression levels of important cell adhesion molecules involved in migration and invasiveness. The rGO flakes, particularly rGO/ATS and rGO/TUD, were found highly toxic. The migration potential of both U87 and Hs5 cells decreased, especially after rGO/TUD treatment. A post-treatment decrease in mobility and FAK expression was observed in U87 cells treated with rGO/ATS and rGO/TUD flakes. The rGO/TUD treatment also reduced β-catenin expression in U87 cells. Our results suggest that rGO flakes reduce the migration and invasiveness of U87 tumor cells and can, thus, be used as potential antitumor agents. [ABSTRACT FROM AUTHOR]

Viscoelastic properties of hydrogels such as stress relaxation or plasticity have been recognized as important mechanical cues that dictate the migration, proliferation, and differentiation of embedded cells. Stress relaxation rates in conventional hydrogels are usually much slower than cellular processes, which impedes rapid cellularization of these elastic networks. Colloidal hydrogels assembled from nanoscale building blocks may provide increased degrees of freedom in the design of viscoelastic hydrogels with accelerated stress relaxation rates due to their strain-sensitive rheology which can be tuned via interparticle interactions. Here, we investigate the stress relaxation of colloidal hydrogels from gelatin nanoparticles in comparison to physical gelatin hydrogels and explore the particle interactions that govern stress relaxation. Colloidal and physical gelatin hydrogels exhibit comparable rheology at small deformations, but colloidal hydrogels fluidize beyond a critical strain while physical gels remain primarily elastic independent of strain. This fluidization facilitates fast exponential stress relaxation in colloidal gels at strain levels that correspond to strains exerted by cells embedded in physiological extracellular matrices (10-50%). Increased attractive particle interactions result in a higher critical strain and slower stress relaxation in colloidal gels. In physical gels, stress relaxation is slower and mostly independent of strain. Hence, colloidal hydrogels offer the possibility to modulate viscoelasticity via interparticle interactions and obtain fast stress relaxation rates at strains relevant for cell activity. These beneficial features render colloidal hydrogels promising alternatives to conventional monolithic hydrogels for tissue engineering and regenerative medicine. In the endeavor to design biomaterials that favor cell activity, research has long focused on biochemical cues. Recently, the time-, stress-, and strain-dependent mechanical properties, i.e. viscoelasticity, of biomaterials has been recognized as important factor that dictates cell fate. We herein present the viscoelastic stress relaxation of colloidal hydrogels assembled from gelatin nanoparticles, which show a strain-dependent fluidization at strains relevant for cell activity, in contrast to many commonly used monolithic hydrogels with primarily elastic behavior. [Display omitted] [ABSTRACT FROM AUTHOR]

Long-timescale viscoelasticity caused by collective cell migration (CCM) significantly influences cell rearrangement and induces generation of mechanical waves. The phenomenon represents a product of the active turbulence occurring at low Reynolds number. The generation of mechanical waves has been a subject of intensive research primarily in 2D multicellular systems, while 3D systems have not been considered in this context. The aim of this contribution is to discuss the generation of mechanical waves during 3D CCM in two model systems: (1) the fusion of two-cell aggregates and (2) cell aggregate rounding after uni-axial compression, pointing out that mechanical waves represent a characteristic of CCM in general. Such perturbations are also involved in various biological processes, such as embryogenesis, wound healing and cancer invasion. The inter-relation between the viscoelasticity and the appearance of active turbulence remains poorly understood even in 2D. The phenomenon represents a consequence of the competition between the viscoelastic force and the surface tension force which induces successive stiffening and softening of parts of multicellular systems. The viscoelastic force is a product of the residual cell stress accumulation and its inhomogeneous distribution caused by CCM. This modeling consideration represents a powerful tool to address the generation of mechanical waves in CCM towards an understanding of this important but still controversial topic. [ABSTRACT FROM AUTHOR]

Abstract Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live‐cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases‐2 and ‐9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell‐mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal‐regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments.

The working electrode's surface property is crucial to cell adhesion and signal collection in electric cell-substrate impedance sensing (ECIS). To date, the indium tin oxide (ITO)-based working electrode is of interest in ECIS study due to its high transparency and biocompatibility. Of great concern is the impedance signal loss, distortion, and data interpretation conflict profoundly created by the movement of multiple cells during ECIS study. Here, a carboxyl-terminated ITO substrate was prepared by stepwise surface amino silanization, with N-hydroxy succinimide (NHS) and 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) treatment, respectively. We investigated the stepwise changes in the property of the treated ITO, cell-substrate adhesion, collective cell mobility, and time course of change in absolute impedance from multiple Chinese hamster ovary (CHO) cells [(Dt-DjZj)CELLS]. The carboxyl-terminated ITO substrate with a surface roughness of 6.37nm shows enhanced conductivity, 75% visible light transparency, improved cell adherence, reduced collective cell migration speed by approximately twofold, and diminished signal distortion in the [(Dt-DjZj)CELLS]. Thus, our study provides an ITO surface-treatment strategy to reduce multiple cell movement effects and to obtain essential cell information from the ECIS study of multiple cells through undistorted (Dt-DjZj)CELLS. [ABSTRACT FROM AUTHOR]

Euglenoids present the ability to alter the shape of their bodies, a process referred to as metaboly. Metaboly is usually used by phagotrophic cells to engulf their prey. However, Euglena gracilis is osmotrophic and photosynthetic. Though metaboly was discovered centuries ago, it remains unclear why E. gracilis undergo metaboly and what causes them to deform, and some consider metaboly to be a functionless ancestral vestige. Here, we discover that flagellum malfunctions trigger metaboly and metaboly is a smart escape strategy adopted by E. gracilis when the proper rotation and beating of the flagellum are hindered by restrictions including surface obstruction, sticking, resistance, or limited space. Metaboly facilitates escape in five ways: (i) detaching the body from the surface; (ii) enlarging the space between flagellum and the restricting surface which restores beating and rotation of the flagellum; (iii) decreasing the torque of viscous resistance for rotation of the body; (iv) decreasing the length of the body; and (v) crawling backwards on a surface or swimming backwards if the flagellum completely malfunctions or has broken off. Our findings suggest that metaboly plays a key role in enabling E. gracilis to escape from harmful conditions when flagellar functions are impaired or absent. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of cancer death in women mainly due to metastasis, which is closely related to cancer stemness. Evidence has shown that cancer stem-like cells (CSCs), which are responsible for cancer stemness, can be decreased by activating dopamine D1 receptor (D1DR). In the present study, we aimed to explore the pharmacological effects as well as the underlying mechanisms of QAP21, a newly synthesized compound that can be orally administered, in metastatic breast cancer cells. Our results showed that QAP21 dose-dependently inhibited the ability of colony formation in 4T1 and MDA-MB-231 cells. Cell mobility, including cell migration and invasion, was also remarkably inhibited. Besides, QAP21 significantly inhibited mammosphere formation and decreased CSC proportion, indicating reduced cancer stemness. We further verified that the nuclear factor-kappa B (NF-κB)/Akt/epithelial-mesenchymal transition (EMT) pathway was markedly impacted by QAP21 treatment. Moreover, QAP21 up-regulated the expressions of D1DR and its second messengers, including cAMP and cGMP, which can be increased when D1DR is activated. SCH 23390, a specific D1DR antagonist, partially or completely reversed the above-mentioned effects of QAP21, indicating that D1DR activation might be involved in the underlying mechanism of QAP21. In summary, QAP21 effectively reduced breast cancer stemness and cell mobility, indicating its potential use for metastatic breast cancer therapy. [ABSTRACT FROM AUTHOR]

Matrix stiffness is a driver of breast cancer progression and mechanosensitive transcriptional activator YAP plays an important role in this process. However, the interplay between breast cancer and matrix stiffness, and the significance of this interplay remained largely unknown. Here, we showed an increase in YAP nuclear localization and a higher proliferation rate in both highly metastatic MDA-MB-231 cells and the non-metastatic counterpart MCF-7 cells when they were exposed to the stiff matrix. However, in response to the stiff matrix highly metastatic MDA-MB-231 cells instead of MCF-7 cells exhibited upregulated mobility, which was shown to be YAP-dependent. Consistently, MDA-MB-231 cells exhibited different focal adhesion dynamics from MCF-7 cells in response to matrix stiffness. These results suggested a YAP-dependent mechanism through which matrix stiffness regulates the migratory potential of metastatic breast cancer cells.

Abstract Background Gastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate. Approximately 40% of patients are refractory to chemotherapy. Currently, the anti-HER2 therapy is the only clinically employed targeted therapy. However, only 7% patients in Taiwan are HER2-positive. Identifying candidate target genes will facilitate the development of adjuvant targeted therapy to increase the efficacy of gastric cancer treatment. Methods Clinical specimens were analyzed by targeted RNA sequencing to assess the expression levels of target genes. Statistical significance of differential expression and correlation between specimens was evaluated. The correlation with patient survival was analyzed as well. In vitro cell mobility was determined using wound-healing and transwell mobility assays. Results Expression of BMP1, COL1A1, STAT3, SOX2, FOXA2, and GATA6 was progressively dysregulated through the stages of gastric oncogenesis. The expression profile of these six genes forms an ubiquitously biomarker signature that is sufficient to differentiate cancer from non-cancerous specimens. High expression status of BMP1 correlates with poor long-term survival of late-stage patients. In vitro, suppression of BMP1 inhibits the mobility of the gastric cancer cell lines, indicating a role of BMP1 in metastasis. Conclusions BMP1 is upregulated in gastric cancer and is correlated with poor patient survival. Suppression of BMP1 reduced gastric cancer mobility in vitro. Our finding suggests that anti-BMP1 therapy will likely augment the efficacy of standard chemotherapy and improve the treatment outcome.

Background: We previously demonstrated that ovarian high grade serous carcinomas (OHGSeCa) and ovarian clear cell carcinomas (OCCCa) with an HNF-1β+/p53+/ARID1A+ immunophenotype were associated with the worst unfavorable prognosis. To clarify the molecular mechanisms underlying this finding, we focused on alterations in the p53 signaling pathway in these tumors. Methods: Changes in cell phenotype and function following knockdown of wild-type p53 (p53-KD) were assessed using OCCCa cells expressing endogenous HNF-1β and ARID1A. The prognostic significance of molecules that were deregulated following p53-KD was also examined using 129 OCCCa/OHGSeCa cases. Results: p53-KD cells had increased expression of Snail, phospho-Akt (pAkt), and pGSK3β, and decreased E-cadherin expression, leading to epithelial-mesenchymal transition (EMT)/cancer stem cell (CSC) features. The cells also exhibited acceleration of cell motility and inhibition of cell proliferation and apoptosis. Next generation sequencing revealed that fibronectin (FN) expression was significantly increased in the p53 KD-cells, in line with our observation that wild-type p53 (but not mutant p53) repressed FN1 promoter activity. In addition, treatment of OCCCa cells with FN significantly increased cell migration capacity and decreased cell proliferation rate, independent of induction of EMT features. In clinical samples, FN/p53 scores were significantly higher in OCCCa/OHGSeCa with the HNF-1β+/p53+/ARID1A+ immunophenotype when compared to others. Moreover, high FN/high p53 expression was associated with the worst overall survival and progression-free survival in OCCCa/OHGSeCa patients. Conclusion: These findings suggest that upregulation of FN following loss of p53 function may impact the biological behavior of OCCCa/OHGSeCa, particularly in tumors with an HNF-1β+/p53+/ARID1A+ immunophenotype, through alterations in cell mobility and cell proliferation. The accompanying induction of EMT/CSC properties and inhibition of apoptosis due to p53 abnormalities also contribute to the establishment and maintenance of tumor phenotypic characteristics. Video Abstract [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live‐cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases‐2 and ‐9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell‐mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal‐regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments. [ABSTRACT FROM AUTHOR]

Ovarian cancer has the highest mortality rate among all gynecological cancers with its pathogenic mechanisms largely unknown. Here, we uncovered that ovarian cancer tissues exhibit higher heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) expression than normal ovarian epithelium tissues. Increased hnRNPA2B1 level matches along with poor prognosis of ovarian cancer patients. Importantly, hnRNPA2B1 inhibition hampers growth, reduces mobility of ovarian cancer cells in vitro and hinders xenograft tumor formation in vivo. Transcriptome profiling analysis reveals that hnRNPA2B1 dictates the expression of various important genes involved in tumorigenesis and Lin-28 Homolog B (Lin28B) is down-regulated upon hnRNPA2B1 loss. hnRNPA2B1 regulates expression of Lin28B via binding to Lin28B mRNA and enhancing its stability. Furthermore, knockdown of Lin28B reduces proliferation and mobility of ovarian cancer cells and impairs tumorigenesis in vivo, whereas Lin28B overexpression promotes xenograft tumor formation. Finally, re-expression of Lin28B in hnRNPA2B1 knockdown cells results in rescued phenotypes. Collectively, our results demonstrate that hnRNPA2B1 facilitates the malignant phenotype of ovarian cancer through activating Lin28B expression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present studies indicate that circRNAs play pivotal roles in human cancers. Lung adenocarcinoma (LUAC), one of lung cancer types, has high metastasis rate. Herein, we focused our study on the function and mechanism of circular RNA circCRIM1 in LUAC development. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circCRIM1, miR-125b-5p, and BTG anti-proliferation factor 2 (BTG2). Transwell assay was carried out to assess cell migration and invasion. The protein levels of BTG2, EMT markers, and HK2 were measured by Western blot. Glycolysis was analyzed through determining glucose consumption and lactate production. Furthermore, the targets of circCRIM1 and miR-125b-5p were predicted and verified by starBase and the dual-luciferase reporter assay, respectively. Also, whether circ-CRIM1 affecting tumor growth in vivo was explored using mouse xenograft assay. RESULTS: CircCRIM1 and BTG2 were downregulated, and miR-125b-5p was upregulated in LUAC tissues/cells. CircCRIM1 upregulation inhibited LUAC cell migration, invasion, epithelial-mesenchymal transition (EMT), glycolysis, and tumor growth. Moreover, circCRIM1 regulated LUAC cell development through targeting miR-125b-5p. MiR-125b-5p affected LUAC cell growth via binding to BTG2. Also, circCRIM1 promoted BTG2 expression by inhibiting miR-125b-5p expression in LUAC cells. CONCLUSIONS: CircCRIM1 was lowly expressed in LUAC. Moreover, circCRIM1 functioned as a sponge of miR-125b-5p to improve BTG2 expression, thereby suppressing LUAC development. Our finding indicated that circCRIM1 could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients. [ABSTRACT FROM AUTHOR]

3-Bromopyruvate (3-BP), an alkylating agent and a glycolytic inhibitor, is a promising anticancer agent, which can be efficient also against multidrug-resistant cancer cells. The aim of this study was to examine how 3-BP affects the survival and mobility of rat (MAT-LyLu and AT-2) and human (DU-145 and PC-3) metastatic prostate cancer cell lines. Cytotoxicity was estimated with Neutral Red. Cell mobility was analyzed by time-lapse microscopic monitoring of trajectories of individual cells at 5-min intervals for 6 h. ATP was estimated with luciferin/luciferase and glutathione (GSH) with o -phthalaldehyde. Actin cytoskeleton was visualized with phalloidin conjugated with Atto-488. All metastatic prostate cell lines studied were very sensitive to 3-BP (IC 50 of 4–26 μM). 3-Bromopyruvate drastically reduced cell movement even at concentrations of 5–10 μM after 1 h treatment. This compound depleted also cellular ATP and GSH, and disrupted actin cytoskeleton. The data obtained suggest that 3-BP can potentially be useful for treatment of metastatic prostate cancer and, especially, be efficient in limiting metastasis. [ABSTRACT FROM AUTHOR]

Dysregulation of microRNA (miRNA) is actively involved in the development and progression of gastric cancer (GC). MiR‐520c was previously found to be overexpressed in GC specimens and cells. However, the clinical significance of miR‐520c and its biological function in GC remain largely unknown. Here, we found that miR‐520c expression in GC tissues was significantly increased compared to normal adjacent gastric tissues. Its increased level was prominently correlated with poor clinical parameters and prognosis of GC patients. Accordingly, the expression of miR‐520c was obviously elevated in GC cell lines as compared with gastric epithelial cells. Overexpression of miR‐520c in N‐87 cells significantly increased the proliferative ability, migration, and invasion of cancer cells, while miR‐520c silencing suppressed MKN‐45 cell proliferation, migration, and invasion in vitro. Mechanically, miR‐520c inversely regulated interferon regulatory factor 2 (IRF2) abundance in GC cells. Herein, IRF2 was found to be a downstream target of miR‐520c in GC. Furthermore, IRF2 was down‐regulated in GC tissues compared to nontumor tissues. An inverse correlation between IRF2 and miR‐520c expression was observed in GC cases. Taken together, miR‐520c may serve as a prognostic predictor and a therapeutic target for GC patients.

Dysregulation of micro RNA (mi RNA) is actively involved in the development and progression of gastric cancer ( GC). MiR-520c was previously found to be overexpressed in GC specimens and cells. However, the clinical significance of miR-520c and its biological function in GC remain largely unknown. Here, we found that miR-520c expression in GC tissues was significantly increased compared to normal adjacent gastric tissues. Its increased level was prominently correlated with poor clinical parameters and prognosis of GC patients. Accordingly, the expression of miR-520c was obviously elevated in GC cell lines as compared with gastric epithelial cells. Overexpression of miR-520c in N-87 cells significantly increased the proliferative ability, migration, and invasion of cancer cells, while miR-520c silencing suppressed MKN-45 cell proliferation, migration, and invasion in vitro. Mechanically, miR-520c inversely regulated interferon regulatory factor 2 ( IRF2) abundance in GC cells. Herein, IRF2 was found to be a downstream target of miR-520c in GC. Furthermore, IRF2 was down-regulated in GC tissues compared to nontumor tissues. An inverse correlation between IRF2 and miR-520c expression was observed in GC cases. Taken together, miR-520c may serve as a prognostic predictor and a therapeutic target for GC patients. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of phlomisoside F (PMF) on the proliferation, migration and invasion of human non-small cell lung cancer cell line A549 and explore the possible mechanisms. Methods:The anti-proliferative effect of PMF on A549 cells was determined by CCK-8. Subsequently, migration and invasion were evaluated by Transwell and Transwell with matrigel assays, respectively. Furthermore, cell cycle and apoptosis were assessed by flow cytometry, while the mechanisms of action were determined by Western blotting. Results: PMF exhibited significant anti-proliferative effect on A549 cells in concentration-dependent and time-dependent manners, with half maximal inhibitory concentration (IC50) of 54.51 µM. Treatment with PMF (10, 20 and 40 µM) for 48 h resulted in significantly decreased migration and invasion in A549 cells. In addition, PMF at concentrations of 25, 50 and 75 µM induced cell cycle arrest in G0/G1phase and enhanced cell apoptosis in A549 cells. Furthermore, caspase-3, caspase-9 and Bax protein expressions were up-regulated while Bacl-2 and COX-2 protein expressions were significantly downregulated at 10, 20 and 40 µM concentrations of PMF. Conclusion: PMF suppresses A549 cell growth, migration and invasion. The mechanism may be related to the induction of mitochondria-mediated apoptosis pathway via regulation of caspase-3, caspase-9, Bcl-2 and Bax expressions, and inhibition of PGE2 synthesis by reducing COX-2 expression. [ABSTRACT FROM AUTHOR]

Various insects require intracellular bacteria that are restricted to specialized cells (bacteriocytes) and are transmitted vertically via the female ovary, but the transmission mechanisms are obscure. We hypothesized that, in the whitefly Bemisia tabaci, where intact bacteriocytes (and not isolated bacteria) are transferred to oocytes, the transmission mechanism would be evident as cellular and molecular differences between the nymph (pre-adult) and adult bacteriocytes. We demonstrate dramatic remodelling of bacteriocytes at the developmental transition from nymph to adulthood. This transition involves the loss of cell-cell adhesion, high division rates to constant cell size and onset of cell mobility, enabling the bacteriocytes to crawl to the ovaries. These changes are accompanied by cytoskeleton reorganization and changes in gene expression: genes functioning in cell-cell adhesion display reduced expression and genes involved in cell division, cell motility and endocytosis/exocytosis have elevated expression in adult bacteriocytes, relative to nymph bacteriocytes. This study demonstrates, for the first time, how developmentally orchestrated remodelling of gene expression and correlated changes in cell behaviour underpin the capacity of bacteriocytes to mediate the vertical transmission and persistence of the symbiotic bacteria on which the insect host depends. [ABSTRACT FROM AUTHOR]

This paper concerns a model for tumor cell migration through the surrounding extracellular matrix by considering mass balance phenomena involving the chemical interactions produced on the cell surface. The well-posedness of this model is proven. An asymptotic analysis via a suitable hydrodynamic limit completes the description of the macroscopic behavior. [ABSTRACT FROM AUTHOR]

Background: Membranous tunneling tubes (TTs) are a recently discovered new form of communication between remote cells allowing their electrical synchronization, migration, and transfer of cellular materials. TTs have been identified in the brain and share similarities with neuronal processes. TTs can be open-ended, close-ended or contain functional gap junctions at the membrane interface. Gap junctions are formed of two unapposed hemichannels composed of six connexin (Cx) subunits. There are evidences that Cxs also play channel-independent role in cell adhesion, migration, division, differentiation, formation of neuronal networks and tumorigenicity. These properties of Cxs and TTs may synergetically determine the cellular and intercellular processes. Therefore, we examined the impact of Cxs expressed in the nervous system (Cx36, Cx40, Cx43, Cx45, and Cx47) on: 1) cell mobility; 2) formation and properties of TTs; and 3) transfer of siRNA between remote cells through TTs. Results: We have identified two types of TTs between HeLa cells: F-actin rich only and containing F-actin and a-tubulin. The morphology of TTs was not influenced by expression of examined connexins; however, Cx36-EGFP-expressing cells formed more TTs while cells expressing Cx43-EGFP, Cx45, and Cx47 formed fewer TTs between each other compared with wt and Cx40-CFP-expressing cells. Also, Cx36-EGFP and Cx40-CFP-expressing HeLa cells were more mobile compared with wt and other Cxs-expressing cells. TTs containing Cx40-CFP, Cx43-EGFP, or Cx47 gap junctions were capable of transmitting double-stranded small interfering RNA; however, Cx36-EGFP and Cx45 were not permeable to it. In addition, we show that Cx43-EGFP-expressing HeLa cells and laryngeal squamous cell carcinoma cells can couple to the mesenchymal stem cells through TTs. Conclusions: Different Cxs may modulate the mobility of cells and formation of TTs in an opposite manner; siRNA transfer through the GJ-containing TTs is Cx isoform-dependent. [ABSTRACT FROM AUTHOR]

Most polymer-based biomedical implantable microscale devices have a smooth surface, so that cell seeding is suppressed in the absence of an adhesive material coating on the surface. SU-8 is a negative photoresist, and is widely used for the fabrication of micro-/nanoscale biomedical devices. A physical surface modification technique was introduced in this study to enhance cell viability and mobility on a SU-8 substrate. To characterize cell viability and mobility, four types of SU-8 substrate were prepared: flat bare substrate, poly- l -lysine (PLL)-coated flat bare substrate, nanoporous substrate, and PLL-coated nanoporous substrate. R at pheochromocytoma (PC12) cells were cultured on these substrates, and nerve growth factor (NGF) was added to induce differentiation of the PC12 cells. On the seventh day of cell culture, PC12 cells on the nanoporous SU-8 substrate showed 24.3% cell differentiation (neurite outgrowth) versus 1.1% cell differentiation on the flat bare substrate. It was also found that cells had a tendency to move from a flat surface to a nanoporous region. These cellular activities on the nanoporous SU-8 substrate suggest that nanopores can be used to regulate cellular activities and can be applied to SU-8-based microscale biomedical devices. [ABSTRACT FROM AUTHOR]

Cell migration is an important and fundamental process. It underlies embryonic development, immune responses, and the repair and regeneration of damaged tissues. Impairments to migration are linked with many important diseases, such as tumor metastasis. The direction of migration can be regulated both by extracellular and intracellular factors. In the case of chemical extracellular factors, the directional migration of cells is called chemotaxis. This review presents a current model of the mechanisms selecting the direction of movement of mesenchymal cells, and analogies and comparisons are made with the mechanisms of chemotaxis in well studied ameboid cells. [ABSTRACT FROM AUTHOR]