PMID- 9697873 OWN - NLM STAT- MEDLINE DCOM- 19980819 LR - 20190915 IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 12 IP - 8 DP - 1998 Aug TI - Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells. PG - 1195-203 AB - Hepatocyte growth factor (HGF), also known as scatter factor (SF), is produced by mesenchymal cells, including bone marrow (BM) stromal cells, 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 function of HGF/SF on hemopoietic mononuclear cells (MNC) from patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with circulating blasts. In contrast to results with normal MNC, HGF/SF alone stimulated the proliferation and colony formation of MNC from these patients. MNC from some (4/13) of the AML patients also produced HGF/SF (0.1-0.2 ng/ml/day), while we could not detect HGF/SF in cultures from normal MNC. Furthermore, it appeared that HGF/SF induced migration of leukemic cells in Boyden using KG1a cells as a model for leukemic blasts. The membranes dividing the two compartments of the Boyden chambers were coated with fibronectin. HGF/SF significantly promoted migration 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 normal human hemopoietic progenitor cells, also promoted migration of MNC 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 antibody directed against HGF/SF was added to the BM stroma supernatant, which reduced migration significantly in 2/3 MDS and in 3/6 AML responders to BM stroma supernatant. In conclusion, HGF/SF promotes proliferation and migration of hemopoietic cells from AML and MDS patients in vitro and may therefore contribute to the malignant potential of these cells. FAU - Weimar, I S AU - Weimar IS AD - Division of Immunology, Netherlands Cancer Institute, Amsterdam. FAU - Voermans, C AU - Voermans C FAU - Bourhis, J H AU - Bourhis JH FAU - Miranda, N AU - Miranda N FAU - van den Berk, P C AU - van den Berk PC FAU - Nakamura, T AU - Nakamura T FAU - de Gast, G C AU - de Gast GC FAU - Gerritsen, W R AU - Gerritsen WR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Antigens, CD34) RN - 0 (Fibronectins) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Acute Disease MH - Antigens, CD34/metabolism MH - Bone Marrow Cells/metabolism MH - Cell Adhesion MH - Cell Division MH - Cell Movement MH - Colony-Forming Units Assay MH - Fibronectins/metabolism MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - In Vitro Techniques MH - Leukemia, Myeloid/*metabolism/pathology MH - Myelodysplastic Syndromes/metabolism/pathology MH - Stromal Cells/metabolism EDAT- 1998/08/11 00:00 MHDA- 1998/08/11 00:01 CRDT- 1998/08/11 00:00 PHST- 1998/08/11 00:00 [pubmed] PHST- 1998/08/11 00:01 [medline] PHST- 1998/08/11 00:00 [entrez] AID - 10.1038/sj.leu.2401080 [doi] PST - ppublish SO - Leukemia. 1998 Aug;12(8):1195-203. doi: 10.1038/sj.leu.2401080.