Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor.

Abstract

A human hepatoma cell line synthesizes, as evidenced by metabolic labeling, an endothelial cell mitogen that is found to be mostly cell associated. The hepatoma-derived growth factor (HDGF) has been purified to homogeneity by a combination of Bio-Rex 70, heparin-Sepharose, and reverse-phase chromatography; it is a cationic polypeptide with a molecular weight of about 18,500-19,000. HDGF is structurally related to basic fibroblast growth factor (FGF). Immunological analysis demonstrates that antiserum prepared against a synthetic peptide corresponding to the amino-terminal sequence of basic FGF cross-reacts with HDGF when analyzed by electrophoretic blotting and by immunoprecipitation. Sequence analysis of tryptic fragments demonstrates that HDGF contains sequences that are homologous to both amino-terminal and carboxyl-terminal sequences of basic FGF.

Suramin prevents neovascularisation and tumour growth through blocking of basic fibroblast growth factor activity

“…Importantly however, while the biological functions of bFGF are maintained and enhanced after binding to heparin, the binding with suramin impairs bFGF activity. Since it has been advanced that bFGF plays a key role also in tumour induced neovascularisation (Folkman et al, 1988;Klagsbrun et al, 1986), and, as recently described (Hori et al, 1991;Gross et al, 1990) Suramin was also able to reduce the growth of M5076 tumour transplanted subcutaneously, with the maximal activity seen administering the compound on the first day after tumour transplantation. In this sytem, repeated peritumoural injections of bFGF increased the tumour growth rate, and significantly reduced the tumour-growth inhibitory activity of suramin.…”

“…Several substances of different chemical nature and cellular origin, including growth factors produced by the neoplastic cells themselves, have been described to be involved in tumourinduced neoangiogenesis (Shing et al, 1985;Folkman & Klagsbrun, 1987) by directly and/or indirectly stimulating endothelial cells proliferation and/or migration (Ausprunk & Folkman, 1977). One of the better characterised among such angiogenic factors is basic Fibroblast Growth Factor (bFGF) (Rifkin & Moscatelli, 1989), whose presence in a large number of normal and malignant cells is well established, and that has been implicated as a major contributing factor in both physiological and pathological neovessel formation (Folkman et al, 1988;Klagsbrun et al, 1986;Thompson et al, 1988;Hayek et al, 1987). Since solid tumour growth and progression are strictly dependent from neovessel formation (Folkman et al, 1989;Brem et al, 1977) interfering with this process by counteracting the effect of angiogenic growth factors could represent a novel and selective therapeutic approach to malignancy.…”

Basic fibroblast growth factor transcriptional autoregulation requires EGR-1

“…As a member of the FGF oncogene family which also includes aFGF, int-2, FGF-5, FGF-6, hst/K-FGF and KGF, bFGF has been suggested to play a crucial role in tumor progression. Strong evidence indicates that bFGF functions as an autocrine growth factor to stimulate cell growth and tumorigenesis of gliomas (Gross et al, 1990;Takahashi et al, 1990Takahashi et al, , 1991Takahashi et al, , 1992Stefanik et al, 1991;Ueba et al, 1994) and hepatocellular carcinoma (Lobb et al, 1986;Klagsbrun et al, 1986;Shimoyama et al, 1991). In human gliomas, the expression level of bFGF correlates with the degree of tumor malignancy (Takahashi et al, 1992).…”

Expressions of basic fibroblast growth factor and its receptors and their relationship to proliferation of human hepatocellular carcinoma cell lines

“…[1][2][3][4][5][6][7][8][9] The FGF family has been widely distributed in normal HCC cell line, SK Hep-1, can produce bFGF in vitro. 31 Normal and/or tumor tissues, and they are known to take various hepatocytes do not express the bFGF receptor, FGFR-1, while important roles, e.g., in angiogenesis, tissue regeneration, a hepatoblastoma cell line (HepG2) has been reported to exwound healing, and embryonic development. [10][11][12][13][14][15][16][17] Among the press this receptor.…”