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In patients with meningiomas, the presence of skull invasion is known to be a predictor of aggressive clinical behavior, which may negatively influence patient outcomes. In the present report, we discuss a case of fibrous meningioma with skull invasion. A 42-year-old woman was referred to our department presenting with hyperostosis in the right parietal bone. T1-weighted magnetic resonance imaging with gadolinium enhancement revealed prominent enhancement of the intraosseous lesion and dura mater. Following the removal of the tumor body and bone lesion, we performed immunohistochemical staining for osteopontin (OPN), matrix metalloproteinase- 2 (MMP2), and integrin β-1 (CD29). The tumor body was immunoreactive for OPN and CD29, but not MMP2, whereas, the bone lesion was immunoreactive for all the three antigens. The present case suggests that OPN, MMP2, and CD29 play key regulatory roles in bone invasion. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Unlike endothelium-dependent vasculature, vasculogenic mimicry (VM) is an alternative type of blood supply in tumors that is frequently associated with poor patient outcome. Nectin-4 serves a vital role in the formation and maintenance of adherens junctions; integrin β-1 (ITGB1) promotes tumor invasion, metastasis and VM formation. In the present study, the analysis of nectin-4 mRNA expression in a database of The Cancer Genome Atlas (TCGA) was combined with that of another non-overlapping cohort of 68 patients with CRC. TCGA data were used to examine nectin-4 mRNA expression in CRC and its correlation with the clinicopathological features of patients. Data from the non-overlapping cohort of patients was used to determine nectin-4 and ITGB1 protein expression in CRC by immunohistochemical (IHC) staining. Cluster of differentiation 34/periodic acid-Schiff double staining was performed to validate the presence of VM formation. The association with, and significance of combining nectin-4, ITGB1 protein expression and VM formation for predicting patient prognosis was evaluated. The TCGA dataset demonstrated that nectin-4 mRNA was upregulated in CRC, which was significantly relate to lymph node metastasis (P=0.0017), distant metastasis (P=0.0045), and tumor-node-metastasis (TNM) stage (P=0.0015). Of the 68 patients analyzed by IHC staining, 48 (70.6%) were positive for nectin-4, 46 (67.6%) for ITGB1 and 17 (25%) for VM formation. Nectin-4 protein expression was associated with ITGB1 protein expression (P<0.01) and VM formation (P<0.05). Nectin-4, ITGB1 expression and VM formation were associated with distant metastasis stage (P<0.05) and TNM stage (P<0.05). Based on these findings it was concluded that nectin-4 was upregulated in CRC tissues compared with normal mucosal tissues, and was associated with ITGB1 expression and VM formation. Furthermore, nectin-4 and ITGB1 protein expression, together with VM formation may be used to predict poor prognosis in CRC. [ABSTRACT FROM AUTHOR]

To investigate the association between malignant gestational trophoblastic diseases and aberrant local expression of E-cadherin and integrin β-1 in the context of identifying a method to predict and diagnose malignant gestational trophoblastic diseases at an early stage.We used immunohistochemistry to assess E-cadherin and integrin β-1 expression profiles in normal chorionic villus, hydatidiform mole, and invasive mole.E-cadherin expression gradually decreased from normal tissue to malignant tissue. Staining for E-cadherin was positive in 90% of normal trophoblastic villus in early pregnancy, 80% in benign hydatidiform mole, and 50% in invasive mole. Notably, invasive mole had significantly lower E-cadherin expression than benign mole (P < 0.05). However, there was no significant difference in staining between benign and malignant moles (15% vs 10%, P > 0.05). Integrin β-1 expression was identical in benign hydatidiform mole and malignant mole (90% and 90%), but this value was significantly higher than that in normal trophoblastic villus (40%, both P < 0.05). Moreover, malignant mole staining was significantly higher than in the benign mole (30% vs 15%, P < 0.05).Aberrant expression of E-cadherin and integrin β-1 is closely related to malignant transformation and hydatidiform mole development. Changes in the expression of E-cadherin and integrin β-1 are informative and may improve the early diagnosis of malignant/invasive moles. [ABSTRACT FROM AUTHOR]

223 Ra is an α-emitter approved for the treatment of bone metastatic prostate cancer (PCa), which exerts direct cytotoxicity toward PCa cells near the bone interface, whereas cells positioned in the core respond poorly because of short α-particle penetrance. β1 integrin (β1I) interference has been shown to increase radiosensitivity and significantly enhance external-beam radiation efficiency. We hypothesized that targeting β1I would improve 223 Ra outcome. Methods: We tested the effect of combining 223 Ra and anti-β1I antibody treatment in PC3 and C4-2B PCa cell models expressing high and low β1I levels, respectively. In vivo tumor growth was evaluated through bioluminescence. Cellular and molecular determinants of response were analyzed by ex vivo 3-dimensional imaging of bone lesions and by proteomic analysis and were further confirmed by computational modeling and in vitro functional analysis in tissue-engineered bone mimetic systems. Results: Interference with β1I combined with 223 Ra reduced PC3 cell growth in bone and significantly improved overall mouse survival, whereas no change was achieved in C4-2B tumors. Anti-β1I treatment decreased the PC3 tumor cell mitosis index and spatially expanded 223 Ra lethal effects 2-fold, in vivo and in silico. Regression was paralleled by decreased expression of radioresistance mediators. Conclusion: Targeting β1I significantly improves 223 Ra outcome and points toward combinatorial application in PCa tumors with high β1I expression., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Breast cancer, melanoma and glioblastoma cells undergo cell-mediated aggregation and aggregate coalescence in a transparent 3D Matrigel environment. Cells from normal tissue and non-tumorigenic cell lines do not exhibit these behaviors. Here, 266 monoclonal antibodies (mAbs) demonstrated to interact with a wide variety of membrane, secreted and matrix proteins, have been screened for their capacity to block these tumorigenic cell-specific behaviors in a 3D environment. Remarkably, only six of the 266 tested mAbs exhibited blocking activity, four targeting integrin ß-1, one targeting integrin α-3 and one targeting CD44. Colocalization of integrins ß-1 and α-3 in fixed cells and in live aggregates suggests that the integrin α-3 ß-1 dimer plays a central role in cancer cell aggregation in the 3D environment provided by Matrigel. Our results suggest that blocking by anti-integrin and anti-CD44 mAbs involves interference in cell-cell interactions.