Hepatocyte growth factor is a potent mitogen for normal human pancreas cells in vitro.

BACKGROUND

Little is known regarding the mechanisms that regulate cell proliferation in the exocrine pancreas. The aim of this study was to analyze the effect of growth factors on normal human exocrine pancreas cultures.

EXPERIMENTAL DESIGN

The mitogenic effect of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and other growth factors was examined using [3H]-thymidine uptake assays. The phenotype of the cultures was analyzed using a panel of mAb. c-met expression was determined by immunohistochemistry and Western blotting.

RESULTS

HGF was the most potent mitogen (concentration range 0.1 to 10 ng/ml), although IGF-1, EGF, and platelet-derived growth factor were also mitogenic in some assays. Combinations of HGF+EGF or HGF+IGF-1 were superior to HGF when used at suboptimal concentrations. Proliferative cultures expressed cytokeratins 7, 8, 18, and 19 and the MUC1 mucin, a phenotype characteristic of normal ductal cells. The 170-kDa precursor and 145-beta chain of c-met were detected in cultured cells with rabbit polyclonal antisera raised against synthetic peptides corresponding to the carboxy-terminal domains of the beta chain. c-met was also detected in the apical membrane of ductal cells in normal pancreas tissue but was generally absent from acinar, centroacinar, and islet cells.

CONCLUSIONS

These results suggest that HGF and c-met may play a role in growth regulation in this organ.