Secretion of insulin-like growth factors and their binding proteins by human normal and hyperplastic prostatic cells in primary culture.

Abstract

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disorder of unknown etiology found in men. Because insulin-like growth factors (IGFs) with their binding proteins (IGFBPs) are involved in the control of cellular proliferation, differentiation, and metabolism, we compared their secretion by prostatic epithelial and stromal cells in primary culture from the four different zones of normal prostate and from hyperplastic tissue to assess their contributions to the hyperplastic development. IGF-I could not be detected in the conditioned medium from either epithelial or stromal cells from normal and BPH tissues. IGF-II concentrations were the same in the conditioned medium from the epithelial cells of the different zones of the normal prostate and that of BPH cells. IGF-II concentrations secreted in stromal cell culture medium, however, were higher in the periurethral zone than in the peripheral and central zones. Moreover, in the periurethral zone, stromal cells secreted higher concentrations of IGF-II than did epithelial cells. Also, BPH stromal cells secreted more IGF-II than did BPH epithelial cells. IGFBP-3, IGFBP-2, and IGFBP-4 were all secreted by both epithelial and stromal cells. In contrast, IGFBP-5 was only produced by stromal cells of the periurethral zone of the normal prostate and BPH tissue. IGFBP-3 was predominantly secreted by normal stromal cells of the transitional zone. We observed that BPH stromal cells presented the same pattern of IGF-II and IGFBP production as normal stromal cells of the periurethral zone. These data support the hypothesis that the periurethral zone is the main region of the prostate implicated in the development of BPH. They also suggest that the variability in both IGF-II secretion and the secreted forms of IGFBPs, depending on anatomical location within the organ, may be important for the autocrine regulation of normal and hyperplastic prostate growth.

Prostate Stroma: Physiology

“…IGF-I [20][21][22][23] is functionally homologous to insulin. Its mitogenic effect is due to its ability to facilitate transfer of cells from the G1 to the S phase of the cell cycle.…”

“…Tennant et al [24] found that the source of the IGF receptor ligand in the prostate may be the prostatic stromal cells, since in vitro studies showed that IGF-II is produced by stromal cells but not by normal prostatic epithelial cells. Recent data of Boudon et al [21] suggest that prostate epithelial cells may also be the site of IGF-II production. IGF-I mRNA and protein have been detected in BPH stroma, but no IGF-I mRNA or protein has been found in BPH epithelial cells.…”

Prostate Cancer Risk in Relation to Selected Genetic Polymorphisms in Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3, and Insulin-like Growth Factor-I Receptor

“…Prostatic epithelial and stromal cells express IGF-I receptors (IGF-IR) and are responsive to IGF-I (4)(5)(6). In addition to their involvement in normal cell growth, IGF-IR seem to play a crucial role in tumor transformation and the survival of tumor cells through their interactions with oncogenes and tumor suppressor genes (7), and through regulation of metalloproteinases synthesis and tumor invasion and metastasis (8).…”

Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin‐like growth factor I, insulin‐like growth factor binding protein 3, and insulin

“…9 The transgenic adenocarcinoma prostate model in mice involves elevated prostatic IGF-I mRNA expression that correlates with tumor progression, and serum IGF-I levels in these mice are elevated compared with the levels in nontransgenic animals. 10 It has been shown that prostate cells and tissues contain IGF-I and IGF-II proteins 7,[11][12][13] as well as IGF mRNA, 12,14 -19 IGF-I receptor, 14,15 and IG-FBP-2-IGFBP-6. In addition to the modulation of IGF availability and action, it has been shown that IGFBPs inhibit cellular growth 18,20 -22 and IGF-I receptor activation.…”