Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt and ERK were determined. DI17E6 promoted detachment and inhibited adhesion of PCa cells to several extracellular matrix (ECM) proteins and cells found in the bone microenvironment, but had no impact on cell viability, cell cycle and caspase 3/7 activity. DI17E6 inhibited migration and invasion of PCa cells. Additionally, DI7E6 decreased phosphorylation of FAK, Akt and ERK. These results indicate that inhibition of integrin alpha V with DI17E6 inhibits several pro-metastatic phenotypes of PCa cells and therefore provide a rationale for further evaluation of DI17E6 for diminishing PCa progression. Implications: This work identifies that therapeutic targeting of integrins containing an alpha V integrin unit inhibits cancer progression and thus may be of clinical benefit.
- Received December 6, 2016.
- Revision received March 8, 2017.
- Accepted March 10, 2017.
- Copyright ©2017, American Association for Cancer Research.