α v β 3 Integrin Mediates Radioresistance of Prostate Cancer Cells through Regulation of Survivin.

The α _v β ₃ integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of α _v β ₃ integrin on the radiosensitivity of prostate cancer cells and the molecular mechanism controlling cell survival in response to ionizing radiation (IR) was investigated. Both LNCaP cells stably transfected with α _v β ₃ integrin and PC-3 cells that contain endogenous β ₃ integrin were used. This study demonstrated that α _v β ₃ integrin increases survival of α _v β ₃ -LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of α _v β ₃ integrin in PC-3 cells sensitizes to radiation. Expression of α _v β ₃ integrin in LNCaP cells also enhances anchorage-independent cell growth while knockdown of α _v β ₃ integrin in PC-3 cells inhibits anchorage-independent cell growth. The α _v β ₃ antagonist, cRGD, significantly increases radiosensitivity in both α _v β ₃ -LNCaP and PC-3 cells. Moreover, α _v β ₃ integrin prevents radiation-induced downregulation of survivin. Inhibition of survivin expression by siRNA or shRNA enhances IR-induced inhibition of anchorage-independent cell growth. Overexpression of wild-type survivin in PC-3 cells treated with α _v β ₃ integrin shRNA increases survival of cells upon IR. These findings reveal that α _v β ₃ integrin promotes radioresistance and regulates survivin levels in response to IR. IMPLICATIONS: Future translational research on targeting α _v β ₃ integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.
(©2018 American Association for Cancer Research.)