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      Expression of MACC1 and c-Met in human gastric cancer and its clinical significance

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          Abstract

          Background

          Recent studies have suggested that the metastasis-associated colon cancer1 (MACC1) gene can promote tumor proliferation, invasion and metastasis through an upregulation of c-Met expression. However, its role in gastric cancer is controversial. Our study investigated expression of MACC1 and c-Met in gastric cancer, as well as correlated this with clinicopathological parameters.

          Methods

          Expressions of MACC1 and c-Met protein in a sample of 98 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationships and correlations with clinicopathological features were analyzed.

          Results

          The positive rates of MACC1 and c-Met protein in primary tumors were 61.22% and 59.18%, respectively. A significant correlation was found between expression of MACC1 and c-Met (P<0.05). Expression of the MACC1 protein in gastric cancer tissue was correlated with lymph node metastasis (χ 2 = 10.555,P = 0.001), peritoneal metastasis (χ 2 = 5.694, P = 0.017), and hepatic metastasis (χ 2 = 4.540,P = 0.033), but not with age, gender, tumor size, location, clinical stage or the distant metastases (P>0.05).

          Conclusion

          The positive rate of MACC1 protein expression was related to the protein expression of c-Met. Both had a correlation with the presence of peritoneal metastasis, lymph node metastasis and hepatic metastasis, all of which contribute to a poor prognosis for gastric cancer patients.

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          Most cited references29

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          MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis.

          We identified a previously undescribed gene associated with colon cancer by genome-wide expression analysis in primary and metastatic carcinomas: metastasis-associated in colon cancer-1, MACC1. MACC1 expression in tumor specimens is an independent prognostic indicator of metastasis formation and metastasis-free survival. We show that the gene encoding the hepatocyte growth factor (HGF) receptor, MET, is a transcriptional target of MACC1. MACC1 promotes proliferation, invasion and HGF-induced scattering of colon cancer cells in cell culture and tumor growth and metastasis in mouse models. These phenotypes are lost in cells expressing MACC1 mutants lacking the SH3 domain or the proline-rich motif. For clinical practice, MACC1 will be useful for the identification of poor prognosis subjects with colorectal cancer and is a promising new target for intervention in metastasis formation.
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            Comparative epidemiology of gastric cancer between Japan and China.

            To clarify the similarities and differences in gastric cancer epidemiology between Japan and China. A comprehensive literature search of the PubMed database was performed. The relevant literature published in China was also been cited. Data on incidence and mortality rates in 2008 were obtained from the Cancer Mondial database, published by International Agency for Research on Cancer at http://www-dep.iarc.fr/. Gastric cancer remains a significant public health burden in both Japan and China. The prevalence of Helicobacter pylori (H. pylori) colonization is high in the adult populations of both countries. Accumulating evidence from intervention studies in both countries has shown the effectiveness of H. pylori eradication in reducing gastric cancer incidence. There are differences, however, in many aspects of gastric cancer, including patterns of incidence and mortality, trends in the prevalence of H. pylori infection, H. pylori strains, the magnitude of risk of gastric cancer related to H. pylori infection, and associations with dietary habits. Compared with China, Japan has seen a more rapid decline in H. pylori infection among adolescents. While Japanese cohort studies have dominated the literature concerning the associations between gastric cancer and dietary habits, numerous case-control studies in China suggest a positive association between a high intake of preserved fish and vegetables and gastric cancer risk. There is a need for a multidisciplinary research approach to understand the interactions between various strains of H. pylori, host factors, and other lifestyle and environmental factors in gastric carcinogenesis in both countries. The shared high incidence of gastric cancer and high prevalence of H. pylori, as well as differences in many aspects of gastric cancer, provide an excellent opportunity to establish Sino-Japanese collaborations.
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              Hepatocyte growth factor promotes lymphatic vessel formation and function.

              The lymphatic vascular system plays a pivotal role in mediating tissue fluid homeostasis and cancer metastasis, but the molecular mechanisms that regulate its formation and function remain poorly characterized. A comparative analysis of the gene expression of purified lymphatic endothelial cells (LEC) versus blood vascular endothelial cells (BVEC) revealed that LEC express significantly higher levels of hepatocyte growth factor receptor (HGF-R). Whereas little or no HGF-R expression was detected by lymphatic vessels of normal tissues, HGF-R was strongly expressed by regenerating lymphatic endothelium during tissue repair and by activated lymphatic vessels in inflamed skin. Treatment of cultured LEC with HGF promoted LEC proliferation, migration and tube formation. HGF-induced proliferation of LEC did not require vascular endothelial growth factor receptor-3 activation, and HGF-induced cell migration was partially mediated via integrin alpha-9. Transgenic or subcutaneous delivery of HGF promoted lymphatic vessel formation in mice, whereas systemic blockade of HGF-R inhibited lymphatic function. These results identify HGF as a novel, potent lymphangiogenesis factor, and also indicate that HGF-R might serve as a new target for inhibiting pathological lymphangiogenesis.
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                Author and article information

                Contributors
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central
                1475-2867
                2013
                10 December 2013
                : 13
                : 121
                Affiliations
                [1 ]Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, 730000, PR, China
                [2 ]Shandong Institute of Parasitic Diseases, Jining 272033, PR, China
                [3 ]Department of Surgery, Ningxia Medical University, Yinchuan 750004, PR, China
                Article
                1475-2867-13-121
                10.1186/1475-2867-13-121
                4029370
                24325214
                aecc37ef-9498-4800-9a4b-d1e05ad4b7f2
                Copyright © 2013 Guo et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 May 2013
                : 24 November 2013
                Categories
                Primary Research

                Oncology & Radiotherapy
                gastric cancer,metastasis associated with colon cancer1,c-met,peritoneal metastasis,lymph node metastasis,hepatic metastasis

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