Insulin-like growth factor I secreted from prostate stromal cells mediates tumor-stromal cell interactions of prostate cancer.
Prostate cancer shows high expression of type I insulin-like growth factor (IGF-I) receptor (IGF-IR) and prostate stromal cells (PrSC) produce IGF-I. Although high plasma level of IGF-I is a risk factor of prostate cancer, the significance of the prostate stromal IGF-I in the regulation of prostate cancer remains elusive. Here we show that the stromal IGF-I certainly regulates the development of prostate cancer. Coinoculation of PrSC increased the growth of human prostate cancer LNCaP and DU-145 tumors in severe combined immunodeficient mice. The conditioned medium of PrSC, as well as IGF-I, induced phosphorylation of IGF-IR and increased the growth of LNCaP and DU-145 cells. PrSC, but not LNCaP and DU-145 cells, secreted significant amounts of IGF-I. Coculture with PrSC increased the growth of DU-145 cells in vitro but the pretreatment of PrSC with small interfering RNA of IGF-I did not enhance it. Furthermore, various chemical inhibitors consisting of 79 compounds with approximately 60 different targets led to the finding that only IGF-IR inhibitor suppressed the PrSC-induced growth enhancement of DU-145 cells. Thus, these results show that the prostate stromal IGF-I mediates tumor-stromal cell interactions of prostate cancer to accelerate tumor growth, supporting the idea that the IGF-I signaling is a valuable target for the treatment of prostate cancer.
Kawada
Manabu
M
Drug Development Unit, Numazu Bio-Medical Research Institute, Microbial Chemistry Research Center, Miyamoto, Numazu-shi, Shizuoka, Japan. kawadam@bikaken.or.jp
Inoue
Hiroyuki
H
Masuda
Tohru
T
Ikeda
Daishiro
D
D002450:Cell Communication / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D007334:Insulin-Like Growth Factor I