Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal cancer
| Autor: | Esther A. Beuling, V. J. M. Wielenga, S. T. Pals, Marcel Spaargaren, Cees van Krimpen, Robbert van der Voort, L. Smit, T. E. I. Taher |
|---|---|
| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
C-Met
(Patho)Physiological endocrinological and methabolic aspects [Prevention of disorders in human reproduction] Colorectal cancer Mouse model of colorectal and intestinal cancer medicine.disease_cause Ligands Proto-Oncogene Mas Receptor tyrosine kinase Pathology and Forensic Medicine chemistry.chemical_compound medicine Humans (Patho-)fysiologische endocriene en metabole aspecten. [Preventie van stoornissen in de menselijke voortplanting] Phosphorylation biology Hepatocyte Growth Factor CD44 Heparan sulfate Proto-Oncogene Proteins c-met medicine.disease Prognosis Hyaluronan Receptors chemistry biology.protein Cancer research Hepatocyte growth factor Carcinogenesis Colorectal Neoplasms Tumorimmunology Heparan Sulfate Proteoglycans medicine.drug Regular Articles |
| Zdroj: | American journal of pathology, 157(5), 1563-1573. Elsevier Inc. American Journal of Pathology, 157, 5, pp. 1563-1573 American Journal of Pathology, 157, 1563-1573 |
| ISSN: | 0002-9440 |
| Popis: | In colorectal cancer patients, prognosis is not determined by the primary tumor but by the formation of distant metastases. Molecules that have been implicated in the metastatic process are the proto-oncogene product c-Met and CD44 glycoproteins. Recently, we obtained evidence for functional collaboration between these two molecules: CD44 isoforms decorated with heparan sulfate chains (CD44-HS) can bind the c-Met ligand, the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF). This interaction strongly promotes signaling through the receptor tyrosine kinase c-Met. In the present study, we explored the expression of CD44-HS, c-Met, and HGF/SF in the normal human colon mucosa, and in colorectal adenomas and carcinomas, as well as their interaction in colorectal cancer cell lines. Compared to the normal colon, CD44v3 isoforms, which contain a site for HS attachment, and c-Met, were both overexpressed on the neoplastic epithelium of colorectal adenomas and on most carcinomas. Likewise, HGF/SF was expressed at increased levels in tumor tissue. On all tested colorectal cancer cell lines CD44v3 and c-Met were co-expressed. As was shown by immunoprecipitation and Western blotting, CD44 on these cells lines was decorated with HS. Interaction with HS moieties on colorectal carcinoma (HT29) cells promoted HGF/SF-induced activation of c-Met and of the Ras-MAP kinase pathway. Interestingly, survival analysis showed that CD44-HS expression predicts unfavorable prognosis in patients with invasive colorectal carcinomas. Taken together, our findings indicate that CD44-HS, c-Met, and HGF/SF are simultaneously overexpressed in colorectal cancer and that HS moieties promote c-Met signaling in colon carcinoma cells. These observations suggest that collaboration between CD44-HS and the c-Met signaling pathway may play an important role in colorectal tumorigenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|