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Thyroid cancer incidence is rising annually largely related to enhanced detection and early stage well-differentiated primary tumors. The prognosis for patients with early stage thyroid cancer is outstanding with most patients being cured with surgery. In selected cases, I-131 is administered to treat known or suspected residual or metastatic disease. Even patients with loco-regional metastases typically have an outstanding long-term prognosis, albeit with monitoring and occasional intervention for residual or recurrent disease. By contrast, individuals with distant metastases from thyroid cancer, particularly older patients with larger metastatic burdens and those with poorly differentiated tumors, have a poor prognosis. Patients with metastatic anaplastic thyroid cancer have a particularly poor prognosis. Published clinical trials indicate that transient disease control and partial remissions can be achieved with kinase inhibitor therapy directed toward angiogenic targets and that in some cases I-131 uptake can be enhanced. However, the direct targets of activity in metastatic lesions are incompletely defined and clear evidence that these treatments increase the duration or quality of life of patients is lacking, underscoring the need for improved knowledge regarding the metastatic process to inform the development of new therapies. In this review, we will focus on current data and hypotheses regarding key regulators of metastatic dormancy, metastatic progression, and the role of putative cancer stem cells. [ABSTRACT FROM AUTHOR]

Abstract: Cancer stem cells (CSCs), isolated in renal carcinomas, exhibit tumor-initiating capabilities and pluripotency. No specific CSC markers have been identified so far; therefore, their characterization is mainly based on functional studies. As they are resistant to chemo and radio therapy, renal CSCs may have a relevant role in tumor establishment, progression, and recurrence. CSCs were also shown to contribute to intra-tumor vasculogenesis through an endothelial differentiation and to favor the generation of the pre-metastatic niche through the release of exosomes/microvesicles. [Copyright &y& Elsevier]

Objective: This study has investigated the existence of label-retaining cell and its distribution in gastric cancer, in the hope that this information will assist investigations on gastric cancer stem cells. Methods: The gastric carcinoma cell line BGC-823 was labeled with BrdU in vitro and then engrafted into the right axilla of nude mice, which developed tumors. Label-retaining cells were quantified by immunohistochemical methods. Results: BrdU positive cells constituted about 96% of the cells in xenograft tumors after 10 days. Subsequently, BrdU positive cells gradually decreased, at the 80th day, label-retaining cells steadily occupied about 0.5%. This set of population cell localized in the margin of cancer nests, which had no difference in cellular morpha. Conclusion: The study demonstrates the presence of label-retaining cells in human gastric cancer xenografts in nude mice and the label-retaining cells may be related with cancer stem cells, which are most likely the cause for spread, metastasis and recurrence. [ABSTRACT FROM AUTHOR]

The concept of the existence of a subset of cancer cells with stem cell-like properties, which are thought to play a significant role in tumor formation, metastasis, resistance to anticancer therapies and cancer recurrence, has gained tremendous attraction within the last decade. These cancer stem cells (CSCs) are relatively rare and have been described by different molecular markers and cellular features in different types of cancers. Ten years ago, a novel class of molecules, small non-protein-coding RNAs, was found to be involved in carcinogenesis. These small RNAs, which are called microRNAs (miRNAs), act as endogenous suppressors of gene expression that exert their effect by binding to the 3'-untranslated region (UTR) of large target messenger RNAs (mRNAs). MicroRNAs trigger either translational repression or mRNA cleavage of target mRNAs. Some studies have shown that putative breast cancer stem cells (BCSCs) exhibit a distinct miRNA expression profile compared to non-tumorigenic breast cancer cells. The deregulated miRNAs may contribute to carcinogenesis and self-renewal of BCSCs via several different pathways and can act either as oncomirs or as tumor suppressive miRNAs. It has also been demonstrated that certain miRNAs play an essential role in regulating the stem cell-like phenotype of BCSCs. Some miRNAs control clonal expansion or maintain the self-renewal and anti-apoptotic features of BCSCs. Others are targeting the specific mRNA of their target genes and thereby contribute to the formation and self-renewal process of BCSCs. Several miRNAs are involved in epithelial to mesenchymal transition, which is often implicated in the process of formation of CSCs. Other miRNAs were shown to be involved in the increased chemotherapeutic resistance of BCSCs. This review highlights the recent findings and crucial role of miRNAs in the maintenance, growth and behavior of BCSCs, thus indicating the potential for novel diagnostic, prognostic and therapeutic miRNA-based strategies. [ABSTRACT FROM AUTHOR]

Background The clinical evolution of laryngeal squamous cell carcinoma (SCC) is undetectable with the current staging criteria. To more completely understand the biology of laryngeal SCC, we assessed the expression of the proteins B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and p16. Methods We assessed immunohistochemically the expression of BMI1 and p16 in 25 laryngeal SCCs at different stages. Results High BMI1 expression was detected in 11.7% of glottic tumors and in 50% of supraglottic tumors. No significant differences were observed in the patients' clinical data after they were stratified by the tumor expression of p16. The expression of nuclear BMI1 in the absence of p16 immunoreactivity correlated significantly with the pN status of the primary tumors. Conclusion Nuclear BMI1 expression in the absence of p16 expression seems to characterize a subset of patients with a high risk of developing lymph node metastasis. © 2012 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

The goal of this work was to study cellular mechanisms of tumor progression and metastasizing. As a result of explantation of cells of rat Zajdela ascitic hepatoma, we obtained two transplantable cell cultures-monolayer (ZH-ad) and suspension (ZH-fl)-that differ in levels of cell differentiation and tumorigenicity. By using tumor-specific immune serum, we revealed tumor-associated antigens, synthesis of which is reduced or inhibited in ZH-ad cells, in outer membranes of the ZH-fl cells. Intraperitoneal injection into rat of 0.5-12 × 10 ZH-fl cells leads to development of an ascitic tumor and death of 100% of animals, whereas, in the case of administration of ZH-ad cells, to achieve a tumorigenic effect, the minimal dose needs to be elevated to 20 × 10 cells. Clonogenic analysis of the ZH-fl cells revealed three types of the formed clones-nonadhesive sphere colonies and two types of monolayer clones differing in proliferative potential, shape of colonies, and cell composition. Upon reaching a critical size, the spheres disintegrated, with separation of single cells and islands of different sizes, some of them being attached with monolayer formation. Three clonal cell lines were obtained: 1C as a result of expansion of a spherical clone and 4G and 10E from monolayer clones. We established that there is tumorigenicity of the 1C cell line, which, at a dose of 107 cells, led to the development of ascites and to the death of 50% of animals. The presented results indicate the existence in the ZH-fl cell population of tumor-initiating cells generating spherical clones-floating multicellular islets that, in culturing in the complete growth medium, are partly differentiated and are attached with monolayer formation. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSC) are considered to be a major driver of cancer progression and successful therapies must control CSCs. However, CSC are often less sensitive to treatment and they might survive radiation and/or chemotherapies. In this paper we combine radiation treatment with differentiation therapy. During differentiation therapy, a differentiation promoting agent is supplied (e.g., TGF-beta) such that CSCs differentiate and become more radiosensitive. Then radiation can be used to control them. We consider three types of cancer: head and neck cancer, brain cancers (primary tumors and metastatic brain cancers), and breast cancer; and we use mathematical modeling to show that combination therapy of the above type can have a large beneficial effect for the patient; increasing treatment success and reducing side effects. [ABSTRACT FROM AUTHOR]

The microgel single-cell culture approach we developed to expand tumor stem cells (TSCs) is associated with limited TSC production, which can be attributable to cell viability loss in microgel formation and tumorsphere expansion limitation caused by hydrogel stiffness. In this work, we developed a gel-free single-cell culture array on a microfluidic chip to overcome these issues. The microfluidic chip used in the study has a 16,000 hydrophilic microchamber array, which can capture ∼2000 single cells at a time. After cell capturing, the cell culture chambers were enclosed by forming a chitosan layer through interactions between chitosan and alginate, thus preventing cell loss in the gel-free culture. The hydrophilic coating prevented cell adhesion, so only TSCs with anti-apoptosis and self-renewal properties can survive the harsh culture and form tumorspheres. After a 7 day culture, 19.04% of the HCT116 colon cancer cells formed single-cell-derived tumorspheres with an average size of 46.59 ± 10.58 μm. Compared with the microgel single-cell culture, sphere-forming rate and TSC expansion efficiency were significantly improved by using this gel-free single-cell culture array. After cell culture, the chitosan layer could be destabilized easily, thus allowing recovery of the tumorspheres from the microchip by applying a reverse flow. Approximately 13,600 cells could be obtained in a single culture, which can be used for off-chip cell assays. Flow cytometry analysis indicated high proportions of LGR5(+) and SOX2(+) cells within the single-cell-derived tumorspheres. Moreover, the differentiation experiments confirmed the multi-lineage differentiation potential of single-cell-derived tumorspheres. The gel-free single-cell culture offers a label-free approach to obtain sufficient amounts of TSCs, which is valuable for tumor biology research and the development of TSC-specific therapeutic strategies.

Background: Tumor invasion, a hallmark of malignant gliomas, involves reorganization of cell polarity and changes in the expression and distribution of scaffolding proteins associated with polarity complexes. The scaffolding proteins of the DLG family are usually downregulated in invasive tumors and regarded as tumor suppressors. Despite their important role in regulating neurodevelopmental signaling, the expression and functions of DLG proteins have remained almost entirely unexplored in malignant gliomas., Methods: Western blot, immunohistochemistry, and analysis of gene expression were used to quantify DLG members in glioma specimens and cancer datasets. Over-expression and knockdown of DLG5, the highest-expressed DLG member in glioblastoma, were used to investigate its effects on tumor stem cells and tumor growth. qRT-PCR, Western blotting, and co-precipitation assays were used to investigate DLG5 signaling mechanisms., Results: DLG5 was upregulated in malignant gliomas compared to other solid tumors, being the predominant DLG member in all glioblastoma molecular subtypes. DLG5 promoted glioblastoma stem cell invasion, viability, and self-renewal. Knockdown of this protein in vivo disrupted tumor formation and extended survival. At the molecular level, DLG5 regulated Sonic Hedgehog (Shh) signaling, making DLG5-deficient cells insensitive to Shh ligand. Loss of DLG5 increased the proteasomal degradation of Gli1, underlying the loss of Shh signaling and tumor stem cell sensitization., Conclusions: The high expression and pro-tumoral functions of DLG5 in glioblastoma, including its dominant regulation of Shh signaling in tumor stem cells, reveal a novel role for this protein that is strikingly different from its proposed tumor-suppressor role in other solid tumors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The differentiation stage of tumors is a central aspect in the histopathological classification of solid malignancies. The differentiation stage is strongly associated with tumor behavior, and generally an immature tumor is more aggressive than the more differentiated counterpart. While this is common knowledge in surgical pathology, the contribution of differentiation-related gene expression and functions to tumor behavior is often overlooked in the experimental, tumor biological setting. The mechanisms by which tumor cell differentiation stages are perturbed or affected are poorly explored but have recently come into focus with the introduction.of the tumor stem cell concept. While developmental biologists view the differentiation as a unidirectional event, pathologists and tumor biologists have introduced the concept of dedifferentiation to explain phenotypic changes occurring in solid tumors. In this review we discuss the impact of the tumor cell differentiation stage as used in surgical pathology. We further discuss knowledge gained from exploring the molecular basis of the differentiation and dedifferentiation processes in neuroblastoma and breast cancer, two tumor forms where the tumor cell differentiation concept is used in the clinical diagnostic work and where the tumor stem cell theory has been applied. [ABSTRACT FROM AUTHOR]

Abstract: Tumor stem cells (TSCs) are considered as the “seeds” in tumor development, metastasis and recurrence. Despite the various immunosurveillance mechanisms in the host, TSCs may possess the phenotypic and functional properties to evade host immunosurveillance and immune-mediated rejection in immunologically intact individuals. The mechanisms of TSC recognition and their consequent destruction are actively disturbed by various processes, including altered immunogenicity of TSCs, production of TSC-derived regulatory molecules, and interaction of TSCs with tumor-infiltrating immune cells. In addition to these TSC-mediated mechanisms, the diverse mesenchymal cells and cytokines in the tumor microenvironment are contribute to TSC immune escape. Recent mechanistic studies provide a more comprehensive understanding of TSCs in the biology, prevention, and therapy of solid tumors. This review will focus on the latest findings for mechanisms underlying TSCs’ escape from the attack of immune system. [Copyright &y& Elsevier]

Side population (SP) cells are a rare subset of cells, which can be isolated by dual-wavelength flow cytometry because of their capacity to efflux Hoechst 33342, found in various tissues and cell lines that are highly enriched for stem cell activity. As recent studies have identified stem-cell-like SP cells in many lung cancer tissues and cell lines, this review is intended to find out the relationship between lung cancer SP cells and lung cancer stem cells. [ABSTRACT FROM AUTHOR]

Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Neuroblastoma is a childhood malignancy of the sympathetic neuronal lineage. It is a rare disease, but since it is frequently diagnosed during infancy, neuroblastoma causes life-long medical follow up of those children that survive the disease. It was early recognized that a high tumor cell differentiation stage correlates to favorable clinical stage and positive clinical outcome. Today, highly differentiated tumors are surgically removed and not further treated. Cells of many established human neuroblastoma cell lines have the capacity to differentiate when stimulated properly, and these cell lines have been used as models for studying and understanding central concepts of tumor cell differentiation. One recent aspect of this issue is the observation that tumor cells can dedifferentiate and gain a stem cell-like phenotype during hypoxic conditions, which was first shown in neuroblastoma. Aberrant or blocked differentiation is a central aspect of neuroblastoma genesis. In this review we summarize known genetic and non-genetic events in neuroblastoma that might be coupled to an aberrant sympathetic neuronal differentiation and thereby indirectly influencing tumorigenesis and/or aggressive neuroblastoma behavior. [Copyright &y& Elsevier]

Putative CD133 brain tumor stem cells have been shown to be located in niches and as single cells. This is the first study providing insight into the different phenotypes of CD133 cells in glioblastoma according to localization. Paraffin sections were stained by double immunofluorescence with CD133 and the candidate stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting showed that the CD133 cells in the niches had a significantly higher expression of Sox2, EGFR and nestin compared to CD133 single cells, but only a 3% Ki67 labeling index versus 14% found for CD133 single cells. Only low endothelial cell marker expression was found in the niches or the CD133 tumor areas, while 43% CD133/CD31 and 25% CD133/CD34 single cells were found. CD133 blood vessels within CD133 niches were less proliferative and more often Bmi-1 than CD133 blood vessels outside niches. In conclusion, different CD133 cell phenotypes exist according to the in situ localization, and also the phenotype of CD133 blood vessels vary according to the localization. CD133 niches contain stem-like cells with a lower proliferation index than CD133 single cells, which have an endothelial differentiation profile suggesting a role in angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: We have previously reported the in vitro anti-proliferative effect of 4-thio-uridylate (s4UMP) on OCM-1 uveal melanoma cells. Here, we assessed the efficacy of s4UMP on JY cells. Treatment of JY cells with s4UMP suppressed their colony forming activity and induced apoptosis; healthy human bone marrow granulocyte–macrophage progenitor cells were 14-fold less sensitive to the nucleotide. In vivo effectiveness of s4UMP was determined using xenograft SCID mouse model. s4UMP decreased the cell number and colony forming activity of the total cell content of the femur of SCID mice transplanted with JY cells without affecting the bone marrow of healthy mice. These results suggest that s4UMP alone or in combination with other clinically approved anti-leukemic remedies should be further explored as a potential novel therapeutic agent. [Copyright &y& Elsevier]

Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC. [ABSTRACT FROM AUTHOR]

Abstract: Deciphering molecular pathways involved in the early steps of prostate oncogenesis requires both in vitro and in vivo models derived from human primary tumors. However the few recognized models of human prostate epithelial cancer originate from metastases. To date, very few models are proposed from primary tumors and immortalizing normal human prostate cells does not recapitulate the natural history of the disease. By culturing human prostate primary tumor cells onto human epithelial extra-cellular matrix, we successfully selected a new prostate cancer cell line, IGR-CaP1, and clonally-derived subclones. IGR-CaP1 cells, that harbor a tetraploid karyotype, high telomerase activity and mutated TP53, rapidly induced subcutaneous xenografts in nude mice. Furthermore, IGR-CaP1 cell lines, all exhibiting negativity for the androgen receptor and PSA, express the specific prostate markers alpha-methylacyl-CoA racemase and a low level of the prostate-specific membrane antigen PSMA, along with the prostate basal epithelial markers CK5 and CK14. More importantly, these clones express high CD44, CD133, and CXCR4 levels associated with high expression of α2β1-integrin and Oct4 which are reported to be prostate cancer stemness markers. RT-PCR data also revealed high activation of the Sonic Hedgehog signalling pathway in these cells. Additionally, the IGR-CaP1 cells possess a 3D sphere-forming ability and a renewal capacity by maintaining their CSC potential after xenografting in mice. As a result, the hormone-independent IGR-CaP1 cellular clones exhibit the original features of both basal prostate tissue and cancer stemness. Tumorigenic IGR-CaP1 clones constitute invaluable human models for studying prostate cancer progression and drug assessment in vitro as well as in animals specifically for developing new therapeutic approaches targeting prostate cancer stem cells. [Copyright &y& Elsevier]

Copyright of Der Gynäkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cells with stem cell properties have been isolated from various areas of the postnatal mammalian brain, most recently from the postnatal mouse cerebellum. We show here that inactivation of the tumor suppressor genes Rb and p53 in these endogenous neural stem cells induced deregulated proliferation and resistance to apoptosis in vitro. Moreover, injection of these cells into mice formed medulloblastomas. Medulloblastomas are the most common malignant brain tumors of childhood, and despite recent advances in treatment they are associated with high morbidity and mortality. They are highly heterogeneous tumors characterized by a diverse genetic make-up and expression profile as well as variable prognosis. Here, we describe a novel ontogenetic pathway of medulloblastoma that significantly contributes to understanding their heterogeneity. Experimental medulloblastomas originating from neural stem cells preferentially expressed stem cell markers Nestin, Sox2 and Sox9, which were not expressed in medulloblastomas originating from granule-cell-restricted progenitors. Furthermore, the expression of these markers identified a subset of human medulloblastomas associated with a poorer clinical outcome. [ABSTRACT FROM AUTHOR]

Objective To observe the stem cell properties of human malignant melanoma cells cultured in serum-free medium. Methods Human malignant melanoma A375 cell line was cultured in serum-free medium, and the melanoma sphere cells (sphere group) and common adherent cells (adherent group) were obtained. Cell migration was detected using Transwell chamber. CD20 and CD133 were detected by immunofluorescence. Sixteen BALB/c mice were divided into the experimental group and control group (8 rats in each group), and the sphere cells and the adherent cells of 1 mL (104 ) were injected into the mouse shoulder blade by subcutaneous injection in the sphere and the adherent groups, respectively. The tumor cells were observed and compared between the two groups. Six weeks later, the mice were killed to obtain the tumor tissues. Results A375 cells were seeded in serum-free medium, visible small round ball suspension cells formed and gradually becomes larger, the ball inside the cells were closely connected with good refraction. The cell migration ability and the expression intensity of CD20 and CD133 in the sphere group were higher than those in the adherent group. After 6 weeks of injection, the mice in the experimental group had a large tumor, and no tumor growth was found in the control group. The tumor tissues of the experimental group were stained with HE, and the malignant melanoma was pathologically diagnosed. Conclusions Human malignant melanoma cells cultured in serum-free medium have the characteristics of stem cells with high migration ability and tumorigenesis. High expression of immune markers CD20, CD133 is found and malignant melanoma exists in the tumor stem cells. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSC) have been extensively studied and gained wide popularity due to their therapeutic potential. Spontaneous transformation of MSC, from both human and murine origin, has been reported in many studies. MSC transformation depends on the culture conditions, the origin of the cells and the time on culture; however, the precise biological characteristics involved in this process have not been fully defined yet. In this study, we investigated the role of p53 in the biology and transformation of murine bone marrow (BM)-derived MSC. We demonstrate that the MSC derived from p53KO mice showed an augmented proliferation rate, a shorter doubling time and also morphologic and phenotypic changes, as compared to MSC derived from wild-type animals. Furthermore, the MSC devoid of p53 had an increased number of cells able to generate colonies. In addition, not only proliferation but also MSC differentiation is controlled by p53 since its absence modifies the speed of the process. Moreover, genomic instability, changes in the expression of c-myc and anchorage independent growth were also observed in p53KO MSC. In addition, the absence of p53 implicates the spontaneous transformation of MSC in long-term cultures. Our results reveal that p53 plays a central role in the biology of MSC. [Copyright &y& Elsevier]

Abstract: A small population of TSCs, which form neurospheres and possess the capacity for self-renewal, has been recently identified in adult and pediatric brain tumors. They differentiate into phenotypically diverse populations, including neuronal, astrocytic, and oligodendroglial cells in vitro and recapitulate original tumors in vivo. The understanding of brain TSCs has been greatly advanced by the knowledge of cell proliferation, which contributes to initiate and sustain the malignant phenotype. In this article, the authors summarized the evidence of the presence of TSCs in human brain tumors and emphasized the significance of the proliferative status of TSCs. By analyzing the data, the authors found that CD133+ cell-initiated glioblastomas have a higher proliferation index when compared to CD133− cells-induced glioblastomas. Furthermore, the relationship and difference of cell proliferation between TSCs and normal NSCs were reviewed. Finally, the preliminary evidence that TSCs in malignant brain tumors have more proliferative capacity than stem/progenitor cells in benign brain tumors was discussed. [Copyright &y& Elsevier]

Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi-micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 µM for copper-containing dendron and 11–15 µM for gold-containing dendron) in comparison with temozolomide (IC50 >100 µM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron-based nanoformulations as antitumor entities. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that cancer is a disease in which the persistence of the tumor relies on a small population of tumor-initiating cells, the so called tumor stem cells (TSC). Only these cells are capable of self-renewal and thereby possess the ability for unlimited proliferation. One reason for the inability of conventional tumor treatments to achieve long-term cures seems to be that TSC are resistant to many therapeutic approaches. A detailed characterization of TSC should have a substantial impact on the optimization of therapeutic protocols. While TSC in hematopoietic malignancies have been most intensively studied, subpopulations with stem cell properties have been identified in some solid tumors including breast carcinomas, gliomas and melanomas. In case of melanoma, however, a clear-cut molecular characterization is still pending. Considerable research is needed to establish standard procedures for the isolation of melanoma stem cells to facilitate determining how these cells, critical for tumor persistence and progression, can be effectively eliminated. A pressing question is if melanoma stem cells are in principle sensitive to immunotherapy. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A common assumption of classical neuroscience was that neurons and glial cells were derived from separate pools of progenitor cells and that, once development was completed, no new neurons were produced. The subsequent disproving of the “no new neuron” dogma suggested that ongoing adult neurogenesis was supported by a population of multipotent neural stem cells. Two germinal regions within the adult mammalian brain were shown to contain neural progenitor cells: the subventricular zone (SVZ) along the walls of the lateral ventricles, and the subgranular zone (SGZ) within the dentate gyrus of the hippocampus. Surprisingly, when the primary progenitors (stem cells) of the new neurons in these regions were identified, they exhibited structural and biological markers of astrocytes. The architecture of these germinal regions and the pattern of division of neural stem cells have raised fundamental questions about the mechanism of adult neurogenesis. This review describes studies on the origin of adult neural stem cells, the features distinguishing them from astrocytes in non-germinal regions, and the control mechanisms of the proliferation and differentiation of these cells. Astrocytic adult neural stem cells are part of a developmental lineage extending from the neuroepithelium to radial glia to germinal astrocytes. Adult neural stem cells appear to be strongly influenced by their local microenvironment, while also contributing significantly to the architecture of these germinal zones. However, environment alone does not seem to be sufficient to induce non-germinal astrocytes to behave as neural stem cells. Although emerging evidence suggests that significant heterogeneity exists within populations of germinal zone astrocytes, the way that these differences are encoded remains unclear. The further characterization of these cells should eventually provide a body of knowledge central to the understanding of brain development and disease. [ABSTRACT FROM AUTHOR]

Adult stem cells can be identified by label-retaining cell (LRC) approach based on their ability to retain nucleoside analog, such as bromodeoxyuridine (BrdU). We hypothesized that mouse nasopharynx contains a small population of epithelial stem/progenitor cells that may be detected by the LRC technique. To identify LRCs in mice nasopharyngeal epithelia, neonatal mice were intraperitoneally injected with BrdU twice daily for 3 consecutive days. After an 8-week chase, long-term BrdU-labeled LRCs (∼2% of cells) were detected in the adult mice nasopharyngeal epithelia by immunostaining with BrdU antibody and some of LRCs (∼12% of cells) were found to be recruited into the S phase of cell cycle with an additional radioactive thymidine-labeling technique, indicating that the stem cells also divide, most likely asymmetrically. To further investigate whether the LRCs existed in human nasopharyngeal carcinoma (NPC) tissues, three NPC cell lines (5-8F, 6-10B and TMNE) were labeled with BrdU in vitro and then individually engrafted into the back of nude mice, which developed tumors. Again, label-retaining stem cells were found in all the three kinds of NPC xenograft tumors (∼0.3% of cells), around 16% of which were also labeled with radioactive thymidine. Thus, this study has demonstrated for the first time the presence of epithelial LRCs in mouse nasopharyngx and human NPC tissues and these stem-like LRCs are not completely quiescent, as they will be recruited into the cell cycle to participate physiological or pathological process at any moment. More importantly, our data showed that NPC also contained stem cells, which are most likely the cause for NPC spread, metastasis and recurrence. [ABSTRACT FROM AUTHOR]

Analyses of genome orthologs in cancer on the background of tumor heterogeneity, coupled with the recent identification that the tumor propagating capacity resides within a very small fraction of cells (the tumor stem cells-TSCs), has not been achieved. Here, we describe a strategy to explore genetic drift in the mitochondrial genome accompanying varying stem cell dynamics in epithelial ovarian cancer. A major and novel outcome is the identification of a specific mutant mitochondrial DNA profile associated with the TSC lineage that is drastically different from the germ line profile. This profile, however, is often camouflaged in the primary tumor, and sometimes may not be detected even after metastases, questioning the validity of whole tumor profiling towards determining individual prognosis. Continuing mutagenesis in subsets with a mutant mitochondrial genome could result in transformation through a cooperative effect with nuclear genes – a representative example in our study is a tumor suppressor gene viz. cAMP responsive element binding binding protein. This specific profile could be a critical predisposing step undertaken by a normal stem cell to overcome a tightly regulated mutation rate and DNA repair in its evolution towards tumorigenesis. Our findings suggest that varying stem cell dynamics and mutagenesis define TSC progression that may clinically translate into increasing tumor aggression with serious implications for prognosis.Oncogene (2006) 25, 6336–6344. doi:10.1038/sj.onc.1209649; published online 29 May 2006 [ABSTRACT FROM AUTHOR]