Androgen-independent prostate cancer DU145 cells suppress androgen-dependent growth of prostate stromal cells through production of inhibitory factors for androgen responsiveness.
Imbalances in the epithelial-stromal interactions are important in the pathogenesis of prostate cancer. However, we know little about androgenic regulation in the stroma of prostate cancer. We examined the cancer-stromal interaction paying attention to androgen responsiveness of stromal side. In co-culture, PC3 and LNCaP cells did not affect dihydrotestosterone (DHT)-dependent growth of prostate stromal cells (PrSCs), but DU145 cells significantly reduced it. Conditioned medium from DU145 cells (DU145-CM) also inhibited DHT-dependent PrSCs growth, androgen receptor (AR) expression, and prostate specific antigen transcription. Although the inhibitory effect of DU145-CM was not affected by neutralizing antibody against EGF, FGF-2, or TNF-alpha, pretreatment with testosterone-Sepharose partially reduced the inhibitory ability of DU145-CM. These results suggest that DU145 cells produce inhibitory factors for androgen responsiveness, including steroid-binding protein(s), and these may participate in crosstalk between DU145 cells and PrSCs as modulators of androgen.
Minamiguchi
Kazuhisa
K
Institute for Chemotherapy, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, 410-0301, Shizuoka-ken, Japan. imcic@shizuokanet.ne.jp
Kawada
Manabu
M
Someno
Tetsuya
T
Ishizuka
Masaaki
M
D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D013196:Dihydrotestosterone / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D012685:Sepharose / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017077:Culture Media, Conditioned; D011944:Receptors, Androgen; D014409:Tumor Necrosis Factor-alpha; D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D012685:Sepharose; D017430:Prostate-Specific Antigen