THE EFFECTS OF GROWTH-FACTORS ASSOCIATED WITH OSTEOBLASTS ON PROSTATECARCINOMA PROLIFERATION AND CHEMOTAXIS - IMPLICATIONS FOR THE DEVELOPMENT OF METASTATIC DISEASE

The extensive mortality and morbidity associated with prostate cancer is caused by the high prevalence of metastatic disease at the time of diagnosis. The area most frequently involved ill metastatic prostate c ancer is the skeleton. Unlike other cancers, which metastasize to bone and destroy the bone matrix, prostate cancer is unique in that it is osteogenic, resulting in the formation of dense, sclerotic bone with h igh levels of osteoblastic activity. We proposed that factors produced by bone cells may be responsible for the development of prostate carc inoma metastasis. We studied the effects of these growth factors on pr ostate cell proliferation by [H-3]thymidine incorporation and chemotax is by the double-filter chamber method. Three prostate carcinoma cell lines were studied, LNCaP (androgen responsive) and PC-3 and DU-145 (a ndrogen unresponsive). The bone-associated growth factors tested were: insulin-like growth factors I and II(IGF-I, IGF-II), transforming gro wth factor beta, interleukin (IL)-1 beta, IL-6, and tumor necrosis fac tor alpha (TNF-alpha). IGF-I and IGF-II significantly increased prolif eration in all three cell lines, whereas IL-6, TNF-alpha, and IL-1 bet a significantly decreased proliferation. Transforming growth factor be ta induced a biphasic response in proliferation in DU-145 and PC-3 cel ls and produced no response on LNCaP cells. Increased cell chemotaxis occurred in the presence of IGF-I and IGF-II, and decreased cell chemo taxis occurred with the addition of TNF-alpha and IL-1 beta. These dat a indicate that growth factors produced by bone cells alter prostate c arcinoma cell proliferation and chemotaxis and suggest that modulation s of the production of these factors may be a potential therapeutic in tervention in deterring the metastasis of prostate carcinoma to bone.