PURPOSE: The hormonally regulated growth of some human carcinomas represents an important therapeutic target. We report that androgens modulate the angiogenic activity of hormone responsive human prostate cancer. MATERIALS AND METHODS: To define further the critical mechanisms underlying hormone responsiveness we examined the angiogenic mediator, vascular endothelial growth factor messenger (m) RNA and protein in response to androgens in vitro as well as the angiogenic response of xenografts of human prostate cancer after androgen withdrawal in vivo. RESULTS: In vitro androgen deprivation of LnCaP prostate cancer cells led to decreased vascular endothelial growth factor mRNA and protein expression as well as a 5-fold destabilization in vascular endothelial growth factor mRNA transcripts. In addition, androgen withdrawal inhibited the hypoxic induction of vascular endothelial growth factor mRNA. In mice bearing LnCaP tumors castration resulted in a rapid decrease in mRNA expression and markedly reduced tumor neovascularization. CONCLUSIONS: These findings implicate sex steroids as an important stimulus for vascular endothelial growth factor regulation in hormone sensitive tumors and demonstrate the reversal of neovascularization after hormone withdrawal as an early event in the tumor response to therapy.
PURPOSE: The hormonally regulated growth of some humancarcinomas represents an important therapeutic target. We report that androgens modulate the angiogenic activity of hormone responsive humanprostate cancer. MATERIALS AND METHODS: To define further the critical mechanisms underlying hormone responsiveness we examined the angiogenic mediator, vascular endothelial growth factor messenger (m) RNA and protein in response to androgens in vitro as well as the angiogenic response of xenografts of humanprostate cancer after androgen withdrawal in vivo. RESULTS: In vitro androgen deprivation of LnCaP prostate cancer cells led to decreased vascular endothelial growth factor mRNA and protein expression as well as a 5-fold destabilization in vascular endothelial growth factor mRNA transcripts. In addition, androgen withdrawal inhibited the hypoxic induction of vascular endothelial growth factor mRNA. In mice bearing LnCaP tumors castration resulted in a rapid decrease in mRNA expression and markedly reduced tumor neovascularization. CONCLUSIONS: These findings implicate sex steroids as an important stimulus for vascular endothelial growth factor regulation in hormone sensitive tumors and demonstrate the reversal of neovascularization after hormone withdrawal as an early event in the tumor response to therapy.
Authors: Kwanghee Kim; Philip A Watson; Souhil Lebdai; Sylvia Jebiwott; Alexander J Somma; Stephen La Rosa; Dipti Mehta; Katie S Murray; Hans Lilja; David Ulmert; Sebastien Monette; Avigdor Scherz; Jonathan A Coleman Journal: Clin Cancer Res Date: 2018-02-20 Impact factor: 12.531
Authors: Vassiliki Tzelepi; Eleni Efstathiou; Sijin Wen; Patricia Troncoso; Maria Karlou; Curtis A Pettaway; Louis L Pisters; Anh Hoang; Christopher J Logothetis; Lance C Pagliaro Journal: J Clin Oncol Date: 2011-05-23 Impact factor: 44.544
Authors: Markus Letsch; Andrew V Schally; Rebeca Busto; Ana M Bajo; Jozsef L Varga Journal: Proc Natl Acad Sci U S A Date: 2003-01-21 Impact factor: 11.205