Integrin αvβ6 sustains and promotes tumor invasive growth in colon cancer progression

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 alpha v beta 6 and matrix metalloproteinase-9 (MMP-9) was performed on tissue microarrays of 200 spots, including 100 cases of colon tumors. RESULTS: High immunoreactivity for alpha v beta 6 (73.7%; 28/38) and MMP-9 (76.5%; 52/68) was observed in invasive tumor portions. Furthermore, the effects of integrin alpha v beta 6 on tumor invasive growth in nude mice were detected. Tumor invasive growth and high expression of both alpha v beta 6 and MMP-9 were only seen in tumors resulting from WiDr cells expressing alpha v beta 6 in the tumorigenicity assay. Flow cytometry was applied to analyze alpha v beta 6 expression in colon cancer WiDr and SW480 cells. The effects of cell density on alpha v beta 6 expression and MMP-9 secretion were also detected by Biotrak MMP-9 activity assay and gelatin zymography assay. High cell density evidently enhanced alpha v beta 6 expression and promoted MMP-9 secretion compared with low density. CONCLUSION: Integrin alpha v beta 6 sustains and promotes tumor invasive growth in tumor progression via a self-perpetuating mechanism. Integrin alpha v beta 6-mediated MMP-9 secretion facilitates pericellular matrix degradation at high cell density, which provides the basis of invasive growth.