Overexpression and regulation of expression of scatter factor/hepatocyte growth factor in prostatic carcinoma.
OBJECTIVE
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-1beta), 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-1beta (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-1beta, 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.
Zhu
X
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Division of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Humphrey
P A
PA
D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D011467:Prostate / Q000737:chemistry* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017228:Hepatocyte Growth Factor