Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression.
Integrins that contain an integrin αV subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine whether abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin αV impacts, prostate cancer progression. To evaluate this, prostate cancer 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 prostate cancer 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 prostate cancer cells. In addition, DI7E6 decreased phosphorylation of FAK, Akt, and ERK. These results indicate that inhibition of integrin αV with DI17E6 inhibits several prometastatic phenotypes of prostate cancer cells and therefore provide a rationale for further evaluation of DI17E6 for diminishing prostate cancer progression.Implications:This work identifies that therapeutic targeting of integrins containing an αV integrin unit inhibits cancer progression and thus may be of clinical benefit.Mol Cancer Res; 15(7); 875-83. ©2017 AACR.
Department of Urology, University of Michigan, Ann Arbor, Michigan.|Department of Immunology, Tianjin Medical University, Tianjin, China.
Yuan
Y
Jiang
Department of Urology, University of Michigan, Ann Arbor, Michigan.
Jinlu
J
Dai
Department of Immunology, Tianjin Medical University, Tianjin, China.
Zhi
Z
Yao
Department of Urology, University of Michigan, Ann Arbor, Michigan.
Greg
G
Shelley
Department of Urology, University of Michigan, Ann Arbor, Michigan. etkeller@umich.edu.|Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan.
Evan T
ET
Keller
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D018450:Disease Progression; D005109:Extracellular Matrix / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics
D061067:Antibodies, Monoclonal, Humanized; D039564:Integrin alphaV; C000592911:Abituzumab