title: Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Guang-Yun
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Cong-Ying
authors.initials: CY
authors.lastname: Dong
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Xian-Qiang
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Bing-Yang
authors.initials: BY
authors.lastname: Hu
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Yang-Feng
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Yong-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
authors.affiliation: Guang-Yun Yang, Xian-Qiang Wang, Bing-Yang Hu, Yong-Wei Chen, Jia-Hong Dong, Hepatobiliary Department, PLA General Hospital, Beijing 100183, China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Dong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis; D014162:Transfection; D047368:Tumor Burden
chemical_list: C061248:ITGB3 protein, human; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Colonic neoplasms; Integrin αvβ6; Invasive growth; Matrix metalloproteinase-9