PMID- 7693339 OWN - NLM STAT- MEDLINE DCOM- 19931201 LR - 20091119 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 53 IP - 22 DP - 1993 Nov 15 TI - Met expression and sarcoma tumorigenicity. PG - 5355-60 AB - 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. FAU - Rong, S AU - Rong S AD - ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702. FAU - Jeffers, M AU - Jeffers M FAU - Resau, J H AU - Resau JH FAU - Tsarfaty, I AU - Tsarfaty I FAU - Oskarsson, M AU - Oskarsson M FAU - Vande Woude, G F AU - Vande Woude GF LA - eng GR - N01-CO-74101/CO/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Neoplasm) RN - 63231-63-0 (RNA) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - 3T3 Cells/chemistry/metabolism MH - Animals MH - Hepatocyte Growth Factor/*analysis/metabolism MH - Humans MH - Mice MH - Proto-Oncogene Proteins/*analysis MH - Proto-Oncogene Proteins c-met MH - RNA/*analysis MH - RNA, Neoplasm/*analysis MH - Receptor Protein-Tyrosine Kinases/*analysis MH - Sarcoma/*chemistry/metabolism MH - Tumor Cells, Cultured EDAT- 1993/11/15 00:00 MHDA- 1993/11/15 00:01 CRDT- 1993/11/15 00:00 PHST- 1993/11/15 00:00 [pubmed] PHST- 1993/11/15 00:01 [medline] PHST- 1993/11/15 00:00 [entrez] PST - ppublish SO - Cancer Res. 1993 Nov 15;53(22):5355-60.