Overexpression and regulation of expression of scatter factor/hepatocyte growth factor in prostatic carcinoma

• Published in: Urology (Ridgewood, N.J.) N.J.), 2000-12, Vol.56 (6), p.1071-1074
• Main Authors: Zhu, Xiaopei, Humphrey, Peter A
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blotting, Western; Carcinoma - genetics; Carcinoma - metabolism; Gene Expression Regulation, Neoplastic - genetics; Hepatocyte Growth Factor - analysis; Hepatocyte Growth Factor - genetics; Humans; Immunoenzyme Techniques; Male; Medical sciences; Nephrology. Urinary tract diseases; Prostate - chemistry; Prostate - metabolism; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - genetics; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(00)00795-0

Objectives. Scatter factor (hepatocyte growth factor) (SF/HGF) is a multifunctional polypeptide growth factor that has been implicated in tumor proliferation, angiogenesis, invasiveness, and metastasis. Little is known of the expression of SF/HGF in human prostatic carcinoma. The aims of this investigation were to quantitate the level of SF/HGF expression in benign versus malignant human prostatic tissues and to assess regulation of SF/HGF expression by human prostatic stromal myofibroblasts. Methods. We determined the level of SF/HGF expression in 10 human prostatic tissue samples (5 benign, 5 carcinoma) by Western blot analysis. Five purified growth factors—basic fibroblast growth factor (bFGF), interleukin-1beta (IL-1β), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and endothelial growth factor (EGF)—were tested for their capacity to induce SF/HGF expression by a human prostatic stromal myofibroblastic cell line, as assessed by enzyme-linked immunosorbent assay. Supernatant from the normal PrEC prostatic epithelial cell line and the DU 145 carcinoma cell line were assayed for SF/HGF-inducing activity. Results. SF/HGF exhibited a mean fourfold overexpression in carcinoma tissues compared with benign prostatic tissue. Significant stimulation of SF/HGF expression by prostatic stromal myofibroblasts was detected for IL-1β (8.1-fold), PDGF (6.2-fold), bFGF (4.0-fold), VEGF (3.7-fold), and EGF (2.9-fold). DU 145-conditioned media, but not the PrEC-conditioned media, contained SF/HGF-inducing activity, which was determined to include IL-1β, bFGF, and PDGF by antibody-blocking experiments. Conclusions. SF/HGF is overexpressed in human prostatic carcinoma tissues. Prostatic carcinoma cell stimulation of SF/HGF expression by adjacent benign myofibroblastic cells as a type of epithelial–stromal paracrine interaction could potentially influence prostatic carcinoma cell behaviors.