HEPATOCYTE GROWTH FACTOR SCATTER FACTOR (HGF/SF) AFFECTS PROLIFERATION AND MIGRATION OF MYELOID LEUKEMIC-CELLS/

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is produced by mesenchymal cells, including bone marrow (BM) stromal cell s, and has mitogenic and motogenic effects on a variety of cell types. Recently, a role has been assigned to HGF/SF and its receptor, c-MET, in both normal and malignant hemopoiesis. We investigated the functio n of HGF/SF on hemopoietic mononuclear cells (MNC) from patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with c irculating blasts. In contrast to results with normal MNC, HGF/SF alon e stimulated the proliferation and colony formation of MNC from these patients. MNC from some (4/13) of the AML patients also produced HGF/S F (0.1-0.2 ng/ml/day), while we could not detect HGF/SF in cultures fr om normal MNC. Furthermore, it appeared that HGF/SF induced migration of leukemic cells in Boyden using KG1a cells as a model for leukemic b lasts. The membranes dividing the two compartments of the Boyden chamb ers were coated with fibronectin. HGF/SF significantly promoted migrat ion In 3/5 samples of MDS patients and in 5/7 samples of AML patients. Supernatant of human BM stromal cells, which is chemoattractive for n ormal human hemopoietic progenitor cells, also promoted migration of M NC from 4/5 MDS patients and 6/7 AML patients. Since HGF/SF is one of the growth factors produced by BM stromal cells, a neutralizing antibo dy directed against HGF/SF was added to the BM stroma supernatant, whi ch reduced migration significantly in 2/3 MDS and in 3/6 AML responder s to BM stroma supernatant In conclusion, HGF/SF promotes proliferatio n and migration of hemopoietic cells from AML and MDS patients in vitr o and may therefore contribute to the malignant potential of these cel ls.