Integrin α-3 ß-1's central role in breast cancer, melanoma and glioblastoma cell aggregation revealed by antibodies with blocking activity.

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.

Overexpressing (), a homolog of the human tumor suppressor gene , rescues the abnormal phenotype of the mutant.

One possible approach to normalize mutant cells that are metastatic and tumorigenic, is to upregulate a functionally similar homolog of the mutated gene. Here we have explored this hypothesis by generating an overexpressor of (), a homolog of , in mutants, the latter generated by targeted mutagenesis of a human epithelial cell line. Overexpression of normalized phenotypic changes associated with the PTEN mutation.

Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44.

Using unique computer-assisted 3D reconstruction software, it was previously demonstrated that tumorigenic cell lines derived from breast tumors, when seeded in a 3D Matrigel model, grew as clonal aggregates which, after approximately 100 hours, underwent coalescence mediated by specialized cells, eventually forming a highly structured large spheroid. Non-tumorigenic cells did not undergo coalescence. Because histological sections of melanomas forming in patients suggest that melanoma cells migrate and coalesce to form tumors, we tested whether they also underwent coalescence in a 3D Matrigel model.