Evidence for a Role of FGF-2 and FGF Receptors in the Proliferation of Non-Small Cell Lung Cancer Cells

Int J Cancer. 1999 Oct 29;83(3):415-23. doi: 10.1002/(sici)1097-0215(19991029)83:3<415::aid-ijc19>3.0.co;2-y.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cattle
  • Cell Division / drug effects
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / physiology*
  • Humans
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / pathology*
  • Mice
  • RNA, Messenger / analysis
  • Receptors, Fibroblast Growth Factor / analysis
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / physiology*
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Recombinant Proteins
  • Fibroblast Growth Factor 2