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Evidence for a role of FGF‐2 and FGF receptors in the proliferation of non‐small cell lung cancer cells
Author(s) -
Berger Walter,
Setinek Ulrike,
Mohr Thomas,
KindasMügge Ingela,
Vetterlein Monika,
Dekan Gerhard,
Eckersberger Franz,
Caldas Carlos,
Micksche Michael
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991029)83:3<415::aid-ijc19>3.0.co;2-y
Subject(s) - autocrine signalling , paracrine signalling , fibroblast growth factor , cell culture , fibroblast growth factor receptor , biology , cancer research , cell growth , receptor , intracrine , microbiology and biotechnology , intracellular , medicine , endocrinology , biochemistry , genetics
Basic fibroblast growth factor (FGF‐2) has been implicated in the progression of human tumours via both autocrine and paracrine (angiogenic) activities. 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 control 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 correlate with a short doubling time as well as with potent anchorage‐independent growth of NSCLC cell lines. In contrast with control cells, NSCLC cells did not secrete considerable amounts of FGF‐2 into the extracellular space. Expression 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‐producing NSCLC and control cell lines. These cells were sensitive to the proliferative effect of recombinant FGF‐2 (rFGF‐2). In NSCLC cell lines with an enhanced FGF‐2 production, representing the majority studied, FGFR localisation was predominantly intracellular. These cells were insensitive to both the proliferative effect of rFGF‐2 and growth inhibition by FGF‐2‐neutralising antibodies. In contrast, several agents antagonised FGF‐2 intracellularly impaired growth of almost all NSCLC cell lines. Our data suggest a role of FGF‐2 and FGFR in the growth stimulation of NSCLC cells possibly via an intracrine mechanism. Int. J. Cancer 83:415–423, 1999. © 1999 Wiley‐Liss, Inc.