Identification of basic fibroblast growth factor sensitivity and receptor and ligand expression in human colon tumor cell lines

Abstract

Basic fibroblast growth factor (bFGF) has been shown to be mitogenic to many different eukaryotic cell lines of mesodermal and neuroectodermal origin. Addition of exogenous bFGF to the chemically defined media of five characterized human colon tumor cell lines, cultured in the absence of epidermal growth factor (EGF), resulted in stimulation of growth from 24% to 146% in four of five cell lines, as measured by a colorimetric MTT assay. A positive dose-response relationship was observed when colon cells were treated with bFGF concentrations from 1 pM to 1 nM. bFGF showed a cumulative effect with EGF in stimulating the proliferation of colon tumor cells. The growth-inhibitory effect of exogenous transforming growth factor-beta (TGF-beta) on these cells was abolished by bFGF. When colon tumor cells were examined on immunoblots with a fibroblast growth factor (FGF) receptor-specific antibody, bands were detected at apparent molecular weights of 131 and 145 kDa. Conditioned media and cell lysates from the same human colon tumor cell lines were immunoprecipitated with a bFGF-specific antibody. An immunoreactive band was detected that comigrated with authentic human recombinant bFGF (16 kDa). Furthermore, preabsorption of anti-bFGF antibody with authentic ligand blocked immunodetection of the 16 kDa band on immunoblots. Documentation of a bFGF response, receptor, and ligand expression in human colon tumor cell lines is novel, and may represent a more widespread role for FGF that extends to epithelial cells and tumors of endodermal germ layer origin. The expression of both ligand and receptors by these cells indicates that bFGF could be involved in their growth regulation at the autocrine level.

Type II, but not type I, cGMP-dependent protein kinase reverses bFGF-induced proliferation and migration of U251 human glioma cells

“…bFGF is an important angiogenic factor, widely distributed in neoplastic tissues (34). Numerous angiogenic peptides have been identified and their effects on tumor vascularity have also been identified (35)(36)(37)(38). FGF receptors activate several intracellular signaling pathways, including MAP kinase pathways.…”

Differential Expression of the Fibroblast Growth Factor Receptor (FGFR) Multigene Family in Normal Human Adult Tissues

“…Moreover, the aberrant or inappropriate expression of FGFRs in normal human adult tissues, coupled with abundant FGF-1 and FGF-2 in tissues of endodermal, neuroectodermal, and mesenchymal origin may play a critical role in the development and/or progression of a wide range of tumors. Indeed, there is growing evidence implicating the FGF-FGFR multigene families in the pathogenesis of carcinoma of the colon (New and Yeoman 1992), breast (Luqmani et al 1992), prostate (Yan et al 1993), kidney, bladder (Chodak et al 1988;Barritault et al 1991), malignant melanoma (Becker et al 1992), meningioma, and malignant glioma (Takahashi et al 1991), as well as in tumor neovascularisation (Brem et al 1992).…”

Fibroblast growth factor 2 in breast cancer: occurrence and prognostic significance

“…FGF-2 has been detected in a variety of human cancers, including colonic adenocarcinoma (New and Yeoman, 1992), bladder cancer (Allen and Maher, 1993), rhabdomyosarcoma , ovarian cancer (Crickard et al, 1994), pancreatic carcinoma (Leung et al, 1994), renal cell carcinoma (Emoto et al, 1994) and oesophageal carcinoma (lida et al, 1994). Studies of human breast have shown high levels of FGF-2 mRNA in non-malignant breast, with malignant transformation of epithelial cells leading to reduced expression (Luqmani et al, 1992;Anandappa et al, 1994).…”