Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression |
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摘 要: |
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收稿时间: | 2014 Sep 20 |
Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression |
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Authors: | Guang-Yun Yang Sen Guo Cong-Ying Dong Xian-Qiang Wang Bing-Yang Hu Yang-Feng Liu Yong-Wei Chen Jun Niu Jia-Hong Dong |
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Institution: | Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, ChinaSen Guo, Xian-Qiang Wang, Yang-Feng Liu, Jun Niu, Hepatobiliary Department, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, ChinaCong-Ying Dong, The Second People’s Hospital of Huangdao, Qingdao 266400, Shandong Province, China |
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Abstract: | AIM: To detect the mechanism by which colon tumor escapes the growth constraints imposed on normal cells by cell crowding and dense pericellular matrices.METHODS: An immunohistochemical study of integrin αvβ6 and matrix metalloproteinase-9 (MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors.RESULTS: High immunoreactivity for αvβ6 (73.7%; 28/38) and MMP-9 (76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin αvβ6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both αvβ6 and MMP-9 were only seen in tumors resulting from WiDr cells expressing αvβ6 in the tumorigenicity assay. Flow cytometry was applied to analyze αvβ6 expression in colon cancer WiDr and SW480 cells. The effects of cell density on αvβ6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced αvβ6 expression and promoted MMP-9 secretion compared with low density.CONCLUSION: Integrin αvβ6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin ανβ6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth. |
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Keywords: | Colonic neoplasms Integrin α vβ 6 Matrix metalloproteinase-9 Invasive growth |
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