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 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.
Berger
W
W
Institute for Tumour Biology/ Cancer Research, Department of Applied and Experimental Oncology, Vienna University, Vienna, Austria. walter.berger@univie.ac.at
Setinek
U
U
Mohr
T
T
Kindas-Mügge
I
I
Vetterlein
M
M
Dekan
G
G
Eckersberger
F
F
Caldas
C
C
Micksche
M
M
D016475:3T3 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2