TY - JOUR
T1 - α v β 3 integrin mediates radioresistance of prostate cancer cells through regulation of survivin
AU - Wang, Tao
AU - Huang, Jiayi
AU - Vue, Mai
AU - Alavian, Michael R.
AU - Goel, Hira Lal
AU - Altieri, Dario C.
AU - Languino, Lucia R.
AU - FitzGerald, Thomas J.
N1 - Funding Information:
The authors would like to thank Diane Safer, Thomas Lozeau, Marie Marley, Ginette Bailey, and Julie Trifone at the Department of Radiation Oncology for performing radiation and for their effort and patience, which made this study possible. We appreciate Huimin Lu for reading the manuscript and giving helpful suggestions. This work was supported by grants from NIH PO1 CA140043 (to L.R. Languino and D.C. Altieri), by a grant from Our Danny Cancer Fund P00010003300000 (to T. Wang) and ACS-IRG 93-033 (to H.L. Goel). M. Vue was supported by theNIH Summer Research Fellowship program at UMass Medical School. This project was also funded, in part, by a Commonwealth University Research Enhancement Program grant with the Pennsylvania Department of Health (H.R.).
Funding Information:
The authors would like to thank Diane Safer, Thomas Lozeau, Marie Marley, Ginette Bailey, and Julie Trifone at the Department of Radiation Oncology for performing radiation and for their effort and patience, which made this study possible. We appreciate Huimin Lu for reading the manuscript and giving helpful suggestions. This work was supported by grants from NIH PO1 CA140043 (to L.R. Languino and D.C. Altieri), by a grant from Our Danny Cancer Fund P00010003300000 (to T. Wang) and ACS-IRG 93-033 (to H.L. Goel). M. Vue was supported by the NIH Summer Research Fellowship program at UMass Medical School. This project was also funded, in part, by a Commonwealth University Research Enhancement Program grant with the Pennsylvania Department of Health (H.R.).
Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2019/2
Y1 - 2019/2
N2 - 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 β3 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 anchorageindependent cell growth while knockdown of α v β 3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The avb3 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.
AB - 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 β3 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 anchorageindependent cell growth while knockdown of α v β 3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The avb3 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.
UR - http://www.scopus.com/inward/record.url?scp=85060911818&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-18-0544
DO - 10.1158/1541-7786.MCR-18-0544
M3 - Article
C2 - 30266752
AN - SCOPUS:85060911818
SN - 1541-7786
VL - 17
SP - 398
EP - 408
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 2
ER -