INVASIVENESS AND METASTASIS OF NIH 3T3 CELLS INDUCED BY MET-HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR AUTOCRINE STIMULATION
INVASIVENESS AND METASTASIS OF NIH 3T3 CELLS INDUCED BY MET-HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR AUTOCRINE STIMULATION
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DOI：
10.1073/pnas.91.11.4731
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发表时间：
1994-05-24
影响因子：
11.1
通讯作者：
VANDEWOUDE, GF
中科院分区：
文献类型：
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作者：
RONG, S;SEGAL, S;VANDEWOUDE, GF
Met原癌基因产物Met是肝细胞生长因子/分散因子（HGF/SF）的酪氨酸激酶生长因子受体。NIH 3 T3细胞内源性表达HGF/SF，当鼠Met异位表达（Met（mu）细胞）或当人Met和人HGF/SF共表达（HMH细胞）时，NIH 3 T3细胞通过自分泌机制在裸鼠中致瘤。在这里，我们表明，Met（mu）和HMH细胞在体外是侵入性的，并显示出侵入性表型所必需的增强的蛋白酶活性。在实验和自发转移测定中，Met（mu）或HMH细胞转移至肺，但皮下注射的Met（mu）和HMH细胞的较低数量在心脏、隔膜、唾液腺和腹膜后产生侵袭性肿瘤。据报道，Met的表达随着无胸腺裸鼠中肿瘤的传代而增加，并且这些肿瘤外植体在转移测定中显示出增强的活性。NIH 3 T3间充质细胞自分泌介导的Met-HGF/SF信号转导可能为理解转移的生物学过程提供重要的系统。
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 (Met(mu) cells) or when human Met and human HGF/SF are coexpressed (HMH cells). Here, we show that Met(mu) and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype. In experimental and spontaneous metastasis assays, Met(mu) or HMH cells metastasize to the lung, but lower numbers of subcutaneously injected Met(mu) 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.