PMID- 8197126 OWN - NLM STAT- MEDLINE DCOM- 19940627 LR - 20211001 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 91 IP - 11 DP - 1994 May 24 TI - Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. PG - 4731-5 AB - The met protooncogene product, Met, is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). NIH 3T3 cells express HGF/SF endogenously and become tumorigenic in nude mice via an autocrine mechanism when murine Met is expressed ectopically (Metmu cells) or when human Met and human HGF/SF are coexpressed (HMH cells). Here, we show that Metmu and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype. In experimental and spontaneous metastasis assays, Metmu or HMH cells metastasize to the lung, but lower numbers of subcutaneously injected Metmu and HMH cells produced invasive tumors in the heart, diaphragm, salivary gland, and retroperitoneum. It has been reported elsewhere that Met expression increased with tumor passage in athymic nude mice, and these tumor explants show enhanced activity in the metastasis assays. Autocrine-mediated Met-HGF/SF signal transduction in NIH 3T3 mesenchymal cells may provide an important system for understanding the biological process of metastasis. FAU - Rong, S AU - Rong S AD - Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702. FAU - Segal, S AU - Segal S FAU - Anver, M AU - Anver M FAU - Resau, J H AU - Resau JH 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 - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Proto-Oncogene Proteins) 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) RN - EC 3.4.24.- (Collagenases) SB - IM MH - 3T3 Cells MH - Animals MH - Cell Movement MH - Cell Transformation, Neoplastic MH - Collagenases/metabolism MH - Hepatocyte Growth Factor/*physiology MH - Humans MH - Mice MH - Mice, Nude MH - *Neoplasm Invasiveness MH - *Neoplasm Metastasis MH - Phenotype MH - Proto-Oncogene Proteins/*physiology MH - Proto-Oncogene Proteins c-met MH - Receptor Protein-Tyrosine Kinases/*physiology PMC - PMC43862 EDAT- 1994/05/24 00:00 MHDA- 1994/05/24 00:01 PMCR- 1994/11/24 CRDT- 1994/05/24 00:00 PHST- 1994/05/24 00:00 [pubmed] PHST- 1994/05/24 00:01 [medline] PHST- 1994/05/24 00:00 [entrez] PHST- 1994/11/24 00:00 [pmc-release] AID - 10.1073/pnas.91.11.4731 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1994 May 24;91(11):4731-5. doi: 10.1073/pnas.91.11.4731.