Effects of hepatocyte growth factor on differentiation and cMET receptor expression in the promyelocytic HL60 cell line

Abstract

Aim-To determine the effects of hepatocyte growth factor (HGF) on myeloid cell differentiation and cMET expression using the promyelocytic HL60 cell line.Methods-HL60 cells cultured with purified recombinant HGF, dimethyl sulphoxide (DMSO), or 12-O tetradecanoylphorbol-13-acetate (TPA) were immunostained for the differentiation markers, human neutrophil elastase (HNE), cathepsin B, MAC387, or the receptor for hepatocyte growth factor (cMET).Results-HGF treated cells were positive on staining for cathepsin B and MAC387, but were negative for HNE, indicating monocytic differentiation. HGF treated cells had the morphology of monocytes but continued to divide at the same rate as control cells and remained non-adherent. DMSO treated cells were positive for HNE and cell numbers were reduced, confirming myeloid differentiation. TPA treated cells were positive for cathepsin B and MAC387, cell numbers were reduced, and the cells became adherent, confirming terminal monocytic differentiation. Untreated HL60 cells were weakly positive for cMET at the start of the culture period and expression increased after 72 hours. Cells treated with HGF, DMSO, or TPA were also positive for cMET.Conclusions-These data suggest that HGF induced partial monocytic differentiation in HL60 cells. In addition, expression of cMET by HL60 cells occurs at an early stage in myelomonocytic cells and is maintained after differentiation along either the myeloid or monocytic pathways.