Met expression and sarcoma tumorigenicity.
The met protooncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signaling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. However, mouse NIH/3T3 fibroblasts overexpressing Met induce tumor formation in nude mice via an autocrine mechanism (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that human cell lines established from various sarcomas express high levels of activated Met receptor. HGF/SF is also detected in the human sarcoma cell lines but at a reduced level when compared to primary fibroblasts. These properties, high Met expression and reduced ligand levels, are indistinguishable from the properties of NIH/3T3 tumor explant cells overexpressing Met (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992; S. Rong et al., Cell Growth & Differ., 4: 563-569, 1993). Moreover, paraffin-embedded sections of primary tumors from human osteosarcomas, chondrosarcomas, and leiomyosarcoma stain intensely for Met and/or HGF/SF and display extensive tumor cell heterogeneity with regard to both paracrine and autocrine stimulation. On the basis of these findings, we propose that Met-HGF/SF autocrine signaling may contribute to the tumorigenic process in human sarcomas.
Rong
S
S
ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Jeffers
M
M
Resau
J H
JH
Tsarfaty
I
I
Oskarsson
M
M
Vande Woude
G F
GF
D016475:3T3 Cells / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019859:Proto-Oncogene Proteins c-met; D012313:RNA / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D012509:Sarcoma / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D012313:RNA; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases