| REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells. | |
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MedLine Citation:
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PMID: 20126989 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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REG4, the latest member of the regenerating gene family, is overexpressed in inflammatory bowel diseases and gastrointestinal carcinomas. To date, its pathophysiologic role has not been well established. Using HT-29 models, we previously identified REG4 as being overexpressed in colorectal tumor cells displaying a drug-resistance phenotype; some also displayed invasive properties. Thus, we investigated the potential functions of REG4 in biological processes involved in colorectal tumor progression such as cell proliferation, migration and invasion. Colon cancer cells secreting REG4 (HT29-5M21, HT29-5F7 and HT29/REG4-8) or not (HT-29, HT29/CT1 and Caco-2/TC7) were used to analyze the autocrine and paracrine effects of REG4. REG4 was continuously secreted into the culture medium of colon cancer cells. REG4 stimulated cell growth in a paracrine manner after 24 h of treatment. Notably, REG4 promoted migration and invasion of tumor cells in both an autocrine and paracrine manner, and these effects were significantly decreased by concomitant treatment with an anti-REG4 antibody. Using pharmacological inhibitors, we showed that PI3K/Akt, PKAs, PKCs and Rho-like GTPases, but not MAPK, are involved in REG4 invasion signals. In addition, REG4 expression was found to be increased in tissues harboring proliferation and migration properties such as the developing intestine and tissues from inflammatory bowel disease, hyperplastic polyps, adenoma and colorectal cancers. In various situations, REG4 expression was not confined to proliferating cells, regenerating cells or cells of the invasive front of metastatic tumors, suggesting that extracellular REG4 may act on epithelial cells in a paracrine manner. Altogether, our results indicate that REG4 is a multifunctional secreted protein which acts on colorectal cancer cells in an autocrine and paracrine manner. According to its biological functions and tissue expression, REG4 may play an important role in the development and progression of colorectal cancer, as well as in intestinal morphogenesis and epithelium restitution. |
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Authors:
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Louisa Rafa; Anne-Frédérique Dessein; Louise Devisme; David Buob; Stéphanie Truant; Nicole Porchet; Guillemette Huet; Marie-Pierre Buisine; Thécla Lesuffleur |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of oncology Volume: 36 ISSN: 1791-2423 ISO Abbreviation: Int. J. Oncol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-03 Completed Date: 2010-10-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 689-98 Citation Subset: IM |
Affiliation:
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Inserm, U837, Lille F-59045, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cell Movement Cell Proliferation Collagen / chemistry Colon / embryology, pathology Colonic Neoplasms / metabolism* Disease Progression Epithelium / embryology, pathology Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic* Humans Lectins, C-Type / biosynthesis* Mitogens Neoplasm Invasiveness Wound Healing |
| Chemical | |
Reg. No./Substance:
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0/Lectins, C-Type; 0/Mitogens; 0/REG4 protein, human; 9007-34-5/Collagen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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