[Growth factors and prostatic tumors].
Prostate growth factor (PGF) was the first growth factor isolated from the prostate. Because of its proliferative effect on fibroblasts and its affinity for heparin, it was first recognized as belonging to the family of fibroblastic growth factors then identified as bFGF (basic fibroblast growth factor) by Story in 1980. The presence of paracrine signals between the fibromuscular stroma and the epithelial tissue in the prostate were first demonstrated in 1970 by the incapacity of epithelial cells to grow without the presence of mesenchymal tissue. These paracrine relations are established during embryogenesis of the prostate and are required for its development and functional control in the adult. Keratinocyte growth factor (KGF), also called FGF-7, could be a stomal androgen mediator with a mitogenic paracrine effect on the epithelium. Dysregulation of growth factors has been suggested to be involved in the development of prostate tumors in elderly men (benign hypertrophy and cancer of the prostate). FGFs probably play an important role in benign prostate hypertrophy. Several studies have demonstrated an important rise in mRNA levels for these factors in benign hyperplastic tissue compared with "normal" tissue. This increased level would be associated with fibromuscular proliferation in periglandular tissue and could explain, at least in prat, the epithelial hyperplasia often associated with the paracrine stimulating effect. In prostate cancer, different families of growth factors have been associated with acquisition of aggressive tumor functions. The EGF receptor and its ligands, the IGF family, beta TGF and certain neuropeptides could be partially implicated in androgen-independent autocrine growth. Heparin-related growth factors (FGFs, Midkine family), VEGF or endothelin could be more particularly implicated in metastatic progression by stimulating cell motility, angiogenesis and metastatic implantation by a two-way cooperation between the tumor and the stroma in which it is implanted. Several of these factors are found in the blood stream and have been proposed as biological markers of poor prognosis. Knowledge of peptides regulating prostate growth or of growth factor antagonists has led to the concept of antipeptidergic therapy as an adjuvant in antiprostate tumor regiments.
Service d'Urologie, Hôpital St Louis 1, Paris.
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Cussenot
D000368:Aged; D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011944:Receptors, Androgen / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D011944:Receptors, Androgen