Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2015; 21(24): 7457-7467
Published online Jun 28, 2015. doi: 10.3748/wjg.v21.i24.7457
Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression
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
Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China
Sen Guo, Xian-Qiang Wang, Yang-Feng Liu, Jun Niu, Hepatobiliary Department, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Cong-Ying Dong, The Second People’s Hospital of Huangdao, Qingdao 266400, Shandong Province, China
Author contributions: Yang GY and Guo S developed the experiment; Wang XQ, Dong CY and Liu YF carried out most of the analyses; Hu BY, Liu Y and Chen YW participated in the design of the study and helped experiments; Niu J and Yang GY drafted the manuscript; Dong JH conceived and coordinated the study; all authors have read and approved the final manuscript.
Supported by China Postdoctoral Science Foundation, No. 20080441310 and No. 201003781 (partly).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Guang-Yun Yang, Associate Chief Physician, Hepatobiliary Department, PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100183, China. yangguangyun301@163.com
Telephone: +86-10-66938330 Fax: +86-10-66938430
Received: September 20, 2014
Peer-review started: September 21, 2014
First decision: October 14, 2014
Revised: November 27, 2014
Accepted: January 21, 2015
Article in press: January 21, 2015
Published online: June 28, 2015
Processing time: 281 Days and 17.8 Hours
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.

Keywords: Colonic neoplasms; Integrin αvβ6; Matrix metalloproteinase-9; Invasive growth

Core tip: This study is designed to identify the mechanisms by which integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression. Our results suggested that integrin αvβ6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin ανβ6-mediated matrix metalloproteinase-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth.