Expression of hepatocyte growth factor and its receptor c-met in human leukemia-lymphoma cell lines.
Recent studies have shown that hepatocyte growth factor (HGF) is a regulatory protein for the proliferation and differentiation of hematopoietic progenitors. The proto-oncogene c-met encodes a tyrosine kinase receptor that binds HGF. To obtain information about their possible involvement in the pathogenesis of hematopoietic tumors, we have examined the expression of HGF and c-met in a large panel of leukemia-lymphoma cell lines encompassing all major hematopoietic cell lineages. HGF and c-met mRNAs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blotting. The panel of 92 cell lines analyzed comprised seven B-cell precursor, ten B-cell, six plasma cell, 13 T-cell, four natural killer (NK) cell, 16 myelocytic, 12 monocytic, 13 erythroid-megakaryocytic and 11 Hodgkin-anaplastic large cell lymphoma (ALCL) lines. In total 64 (70%) were RT-PCR-positive for HGF and 43 (47%) for c-met. The highest percentages of expression were found for HGF in the plasma cell (100%), NK (100%) and myeloid (75-92%) cell line categories, whereas c-met was found predominantly in plasma cell (100%) and Hodgkin-ALCL (91%) cell lines. The concomitant expression of HGF and c-met in plasma cell lines (100%) and Hodgkin-ALCL (73%) cell lines should be noted. The high HGF expression in myelocytic-monocytic cell lines (75 and 92%) contrasts with the low c-met expression (18 and 8%) in these cell lineages. In 50 cell lines, mRNA expression of these two genes was also examined at the Northern blot level: 12/50 (24%) and 4/48 (8%) were positive for HGF and c-met mRNA expression, respectively. Of note, three of the four c-met + lines belonged to the category Hodgkin-ALCL; the Hodgkin cell line SUP-HD-1 showed both HGF and c-met mRNA bands suggesting the possibility of an autocrine loop. In conclusion, we detected HGF expression in various types of leukemia-lymphoma cell lines, particularly in plasma cell and myeloid malignancies; c-met expression was found in plasma cell and Hodgkin-ALCL cell lines. Further detailed analysis of the role of this ligand-receptor pair in the pathogenesis of hematopoietic neoplasms is indicated; to this end the HGF + and c-met + cell lines described here represent exquisite model systems.
Pons
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E
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig.
Uphoff
C C
CC
Drexler
H G
HG
D004273:DNA, Neoplasm / Q000032:analysis; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met