Elevated expression of FGF-2 does not cause prostate cancer progression inLNCaP cells

BACKGROUND. Androgen-independent (AI) prostate cancer (CaP) resulting from progression of disease is untreatable. Such progression may relate to upreg ulation and autocrinicity of growth factor expression. We studied one candi date growth factor, basic fibroblast growth factor (FGF-2). METHODS. LNCaP cells made autocrine for FGF-2 by stable transfection with F GF-2 were examined for cancer progression, measured by 1) altered response to androgen, 2) ability to grow more quickly when cocultured with bone cell s in vitro or to form tumors when coinoculated with bone cells in vivo, or 3) increase in metastatic ability. RESULTS. Stably transfected lines differed in FGF-2 protein expression. LNC aP-HF (high production of FGF-2) expressed more FGF-2 than LNCaP-LF (low pr oduction of FGF-2); controls were negative. In vitro, compared with LNCaPs, LNCaP-HF cells showed a slightly increased growth rate, reduced proliferat ion in response to androgen but not to estrogen or progesterone, and a decr eased proliferative response to epidermal growth factor (EGF) and FGF-2. Al though giving a slightly faster take rate, LNCaP-HF cells without Matrigel only formed small, fast-regressing tumors in male nude mice, and with Matri gel, did not differ from LNCaPs in growth rate or tumor size. No metastases occurred. No tumors grew in females: Mixed growth of FGF-2 transfectants w ith human fetal osteoblasts failed to cross-stimulate in vitro, or to allow tumor formation in vivo. CONCLUSIONS. Although FGF-2 is overexpressed in AI CaPs, our experiments sh ow that upregulation of FGF-2 expression is not sufficient to cause androge n independence, tumorigenicity, or metastases production (i.e., prostate ca ncer progression) in LNCaP cells. (C) 1999 Wiley-Liss, Inc.