ArticleClinical & experimental metastasis2000
Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis.
Article in Clinical & experimental metastasis, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 45 citations in OpenAlex.
- Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors and MET-positive lung cancer.Investigational new drugs · 2015Trial
- Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors.OncoTargets and therapy · 2014Review
- Suppression of Met activation in human colon cancer cells treated with (-)-epigallocatechin-3-gallate: minor role of hydrogen peroxide.Biochemical and biophysical research communications · 2009Article
- Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer.Neoplasia (New York, N.Y.) · 2009Article
- MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis.Nature medicine · 2009Article
- NK4, an HGF antagonist, prevents hematogenous pulmonary metastasis by inhibiting adhesion of CT26 cells to endothelial cells.Clinical & experimental metastasis · 2009Article
- A positive feedback loop between hepatocyte growth factor receptor and beta-catenin sustains colorectal cancer cell invasive growth.Oncogene · 2007Article
- Transcriptional targets of hepatocyte growth factor signaling and Ki-ras oncogene activation in colorectal cancer.Oncogene · 2006Article
- Impact of laparotomy and liver resection on the peritoneal concentrations of fibroblast growth factor 2, vascular endothelial growth factor and hepatocyte growth factor.Journal of cancer research and clinical oncology · 2006Article
- Collagen type IV, laminin, alpha-smooth muscle actin (alphaSMA), alpha1 and alpha6 integrins expression in the liver with metastases from malignant gastrointestinal tumours.Clinical & experimental metastasis · 2004Article
- Immunoblot analysis of c-Met expression in human colorectal cancer: overexpression is associated with advanced stage cancer.Clinical & experimental metastasis · 2004Article
- Molecular pathology of tumor metastasis III. Target array and combinatorial therapies.Pathology oncology research : POR · 2003Review
- Molecular pathology of tumor metastasis. I. Predictive pathology.Pathology oncology research : POR · 2001Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The organ-specific metastasis characterizes several human cancers, including colon carcinoma, a disease that frequently involves metastases in the liver. The data on the molecular mechanisms of liver metastasis would therefore be highly useful for prognostic purposes. Although the upregulation/amplification of the hepatocyte growth factor (HGF) receptor, c-met, has been frequently observed in colon cancer metastasis, the actual functional significance of the feature in the liver metastatization is not yet known. We have used three human colon carcinoma cell lines (HT29, HT25 and WiDr), characterized by different liver metastatic potentials in SCID mice, to analyze the expression of c-met and the biological effects of HGF. We found that HGF induces scattering in in vitro liver-metastatic cell lines (HT25 and WiDr) only at doses which are non-mitogenic (1-20 ng/ml). Analysis of the c-met expression revealed that the metastatic cell lines express authentic c-met gene and protein material, unlike the non-metastatic HT29 cell line, which expresses only the c-terminal cytoplasmic domain of the c-met beta-chain. Interestingly, c-met was found to be localized in the substrate-attached peripheral membrane and partially colocalized with phosphotyrosine-proteins in the metastatic cells only when kept on fibronectin. On the other hand, we have analyzed 86 primary human colon cancers in Dukes' B (invasive but non-metastatic) and C (invasive and lymph node metastatic) stages. Western blotting of the proteins isolated from the tumor tissues and immunohistochemical control study on the paraffin samples of a third of these cases (25/86) all indicated a significant upregulation of the c-met protein in the Dukes' C tumor glands compared to the Dukes' B stages (P < 0.001 and P < 0.05, respectively). Since the two stages differ in the involvement of the regional lymph nodes but not in the invasion depth, the clinicopathological data and our experimental findings further support the notion that the c-met expression in human colon cancer can be considered as a marker of the metastatic potential due to its involvement in the generation of the motility signal.
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