Insulin-like growth factor I secreted from prostate stromal cells mediates tumor-stromal cell interactions of prostate cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 8; pp. 4419 - 4425
• Main Authors: KAWADA, Manabu, INOUE, Hiroyuki, MASUDA, Tohru, IKEDA, Daishiro
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-04-2006
• Subjects: Antineoplastic agents; Biological and medical sciences; Cell Communication - physiology; Cell Growth Processes - physiology; Cell Line, Tumor; Coculture Techniques; Gynecology. Andrology. Obstetrics; Humans; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - physiology; Insulin-Like Growth Factor I - secretion; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prostate - cytology; Prostate - metabolism; Prostate - secretion; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - secretion; Signal Transduction; Stromal Cells - metabolism; Stromal Cells - pathology; Stromal Cells - secretion; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; Prostate disease; Secretion; Cell cell interaction; Malignant tumor; Stromal cell; Insulin like growth factor 1; Male genital diseases; Urogenital system; Prostate cancer; Stromal tumor
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-4239

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.