title: Suppression of DHT-induced paracrine stimulation of endothelial cell growth by estrogens via prostate cancer cells.
abstract: BACKGROUND
  Androgen modulation of angiogenesis in prostate cancer may be not directly mediated by androgen receptor (AR) as AR is not detected in the prostatic endothelial cells.
  
  
  METHODS
  We examined the paracrine stimulation of cell proliferation by prostate tumor cells and its modulation by androgen and estrogens in a murine endothelial cell line (MEC) that does not express AR.
  
  
  RESULTS
  Tumor cell conditioned media (TCM) collected from LAPC-4 or LNCaP prostatic tumor cells produced a time- and concentration-dependent induction of cell growth in MECs, which was parallel to the VEGF concentration in the TCM. This TCM-induced cell growth in MECs was enhanced by the treatment of prostatic tumor cells with dihydrotestosterone (DHT). Both the TCM-stimulation and DHT-enhancement effects in MECs were completely blocked by SU5416, a specific VEGF receptor antagonist. Co-administration of 17α-estradiol or 17β-estradiol with DHT in prostatic tumor cells completely inhibited the DHT-enhancement effect while treatment with DHT, 17α-estradiol or 17β-estradiol did not produce any significant direct effect in MECs. Moreover, administration of 17α-estradiol or 17β-estradiol in xenograft animals with LAPC-4 or LNCaP prostate tumor significantly decreased the microvessel number in the tumor tissues.
  
  
  CONCLUSIONS
  Our study indicated that prostate tumor cells regulate endothelial cell growth through a paracrine mechanism, which is mainly mediated by VEGF; and DHT is able to modulate endothelial cell growth via tumor cells, which is inhibited by 17α-estradiol and 17β-estradiol. Thus, both17α-estradiol and 17β-estradiol are potential agents for anti-angiogenesis therapy in androgen-responsive prostate cancer.
authors: Department of Medicine/Endocrinology, Weill Cornell Medical College, New York, NY, USA.
authors: Juan
authors: J
authors: Wen
authors: Yuan
authors: Y
authors: Zhao
authors: Jinghe
authors: J
authors: Li
authors: Chunyan
authors: C
authors: Weng
authors: Jingjing
authors: J
authors: Cai
authors: Kan
authors: K
authors: Yang
authors: Hong
authors: H
authors: Yuan
authors: Julianne
authors: J
authors: Imperato-McGinley
authors: Yuan-Shan
authors: YS
authors: Zhu
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
chemical_list: D000728:Androgens; D004967:Estrogens; D007211:Indoles; D011758:Pyrroles; D013196:Dihydrotestosterone; D004958:Estradiol; C116890:Semaxinib; D040262:Receptors, Vascular Endothelial Growth Factor