The effect of bone-associated growth factors and cytokines on the growth of prostate cancer cells derived from soft tissue versus bone metastases in vitro.

Prostate cancer metastasis to bone may be mediated by preferential proliferation of these cells in the bone's microenvironment. We hypothesize that this preferential proliferation is mediated by bone-associated growth factors (GFs) and cytokines. To test our hypothesis, human prostate cancer cells, derived from both soft tissue (LNCaP, DuCaP, DU145) and bone metastases (PC-3, VCaP, MDA-2a, MDA-2b), were treated with bone-associated GFs and cytokines (PDGF, IGF-1, TGF-beta, EGF, bFGF, TNF-alpha, IL-1, and IL-6) for 48 h, and their growth responses were compared. The responses of soft tissue-derived prostate cancer cell lines to bone GFs and cytokines were variable. LNCaP cell growth was stimulated by IGF-1 but was inhibited by TNF-alpha. DU145 cell growth was stimulated with EGF. Prostate cancer cell lines derived from bone metastases also responded variably to bone GFs and cytokines. IL-1 stimulated the growth of MDA-2a and 2b cell lines in a dose-dependent manner. PDGF and bFGF both demonstrated variable effects on bone-derived prostate cancer cell lines. TNF-alpha inhibited proliferation of the VCaP cells. These findings demonstrate that human prostate cancer cell lines derived from bone metastases may not respond preferentially to bone-associated GFs and cytokines.