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

Abstract

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.

• Authors: Daniel F Lusche, Michael R Klemme, Benjamin A Soll, Ryan J Reis, Cristopher C Forrest, Tiffany S Nop, Deborah J Wessels, Brian Berger, Rebecca Glover, David R Soll
• Journal: mAbs (MAbs) 2019 May/Jun Vol. 11 Issue 4 Pg. 691-708 ISSN: 1942-0870 [Electronic] United States
• PMID: 30810437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Blocking
• Antibodies, Monoclonal
• CD44 protein, human
• Drug Combinations
• Hyaluronan Receptors
• Integrin alpha3beta1
• Laminin
• Proteoglycans
• matrigel
• Collagen

Topics

• Antibodies, Blocking (metabolism)
• Antibodies, Monoclonal (metabolism)
• Breast Neoplasms (metabolism, pathology)
• Cell Adhesion
• Cell Aggregation
• Cell Line, Tumor
• Cell Movement
• Collagen
• Drug Combinations
• Female
• Glioblastoma (metabolism, pathology)
• Humans
• Hyaluronan Receptors (immunology, metabolism)
• Integrin alpha3beta1 (immunology, metabolism)
• Laminin
• Melanoma (metabolism, pathology)
• Proteoglycans