Evidence for a role of FGF-2 and FGF receptors in the proliferation of non-small cell lung cancer cells

Basic fibroblast growth factor (FGF-2) has been implicated in the progressi on of human tumours via both aurtocrine and paracrine (angiogenic) activiti es. We investigated the expression of FGF-2 and FGF receptors (FGFR-1 to -4 ) in NSCLC cell lines (N = 16), NSCLC surgical specimens (N = 21) and 2 con trol cell lines. Our data show that almost all NSCLC cells produce elevated levels of FGF-2 and FGFR in vitro and in vivo. FGF-2 expression did correl ate with a short doubling time as well as with potent anchorage-independent growth of NSCLC cell lines. In contrast with control cells, NSCLC cells di d not secrete considerable amounts of FGF-2 into the extracellular space. E xpression levels of FGFR-1 and -2 in NSCLC cell lines correlated with FGF-2 production. FGFR were located at the plasma membranes in some low FGF-2-pr oducing NSCLC and control cell lines. These cells were sensitive to the pro liferative effect of recombinant FGF-2 (rFGF-2). In NSCLC cell lines with a n enhanced FGF-2 production, representing the majority studied, FGFR locali sation was predominantly intracellular. These cells were insensitive to bot h the proliferative effect of rFGF-2 and growth inhibition by FGF-2-neutral ising antibodies. In contrast, several agents antagonised FGF-2, intracellu larly impaired growth of almost all NSCLC cell lines. Our data suggest a ro le of FGF-2 and FGFR in the growth stimulation of NSCLC cells possibly via art intracrine mechanism. (C) 1999 Wiley-Liss, Inc.