EXPRESSION OF HGF SF IN MESOTHELIOMA CELL-LINES AND ITS EFFECTS ON CELL MOTILITY, PROLIFERATION AND MORPHOLOGY/

The expression of hepatocyte growth factor/scatter factor (HGF/SF) was studied in 12 mesothelioma cell lines characterized by either an epit helioid or a fibroblast-like phenotype. Conditioned media from these l ines were analysed by bioassay and ELISA, and HGF/SF was detected in t hree cell lines, all with a fibroblast-like or mixed morphology. None of eight epithelioid cell lines expressed the factor. Thus, for these cell lines, the ability to secrete HGF/SF correlated with the cell phe notype. Following on from these observations, two cell lines, BR and B T, with a fibroblast-like and an epithelioid phenotype, respectively, were further investigated. Both cell lines expressed the Met receptor but only BR secreted HGF/SF. Both cell lines responded to exogenous HG F/SF treatment by a change of morphology but in different ways: BR bec ame more elongated and bipolar, while BT formed more spread-out cell c olonies. HGF/SF acted as a paracrine effector on the epithelioid BT ce lls and stimulated both cell-spreading and proliferation. Interestingl y, BT cells spread but did not scatter in response to exogenous HGF/SF . In contrast BR cells showed only some stimulation of cell motility w ith HGF/SF and no increase in cell proliferation was observed. Because HGF/SF was previously found in the pleural effusion fluids of patient s with malignant mesothelioma and in paraffin-embedded tumour tissues, it is concluded that HGF/SF may well stimulate the growth and spread of malignant mesothelioma in vivo by paracrine and/or autocrine mechan isms.