Enhancement of bFGF export associated with malignant progression of human salivary gland cell clones

Abstract

Using 2 in vitro systems in which normal human salivary gland cells can be immortalized by transfection with SV40 DNA (NS-SV-DC), and in which a non-metastasizing human salivary gland adenocarcinoma cell clone (HSGc) can be converted to biologically aggressive and metastasizing cancer cells, we analyzed the relationship between the expression of basic fibroblast growth factor (bFGF) and malignant phenotype in human salivary gland cell clones. By enzyme immunoassay, intracellular contents of bFGF were equally detected in all the cell clones, while bFGF contained in serum-free conditioned medium of each cell clone was different: HSGc and metastasizing cell clones, respectively, released 2- and 10O-fold more bFGF into media than did NS-SV-DC. Immunoblot analysis also revealed a similar result as that detected by enzyme immunoassay. By Northern blot analysis, bFGF mRNA expression was consistently detected in all the cell clones examined. We then quantitated bFGF contents in sera of tumor-bearing mice by enzyme immunoassay. Although sera from nude mice bearing an HSGc tumor showed significantly higher amounts of bFGF than those of control mice, bFGF concentrations in sera gradually decreased after removal of the tumor. For metastasizing cell clones, serum concentrations of bFGF were 2.2- to 2.6-fold higher than those of HSGc. In addition, bFGF amounts in sera after removal of the tumors were significantly higher in mice bearing metastasizing cell clone tumors compared with those of HSGc tumor-hearing mice. Our results, therefore, indicate that increase in bFGF release occurs along with the progression of human salivary gland cancer cells and that serum bFGF may be useful for evaluation of tumor presence.