Tie2-dependent deletion of α6 integrin subunit in mice reduces tumor growth and angiogenesis

The alpha 6 integrin subunit (alpha 6) has been implicated in cancer cell migration and in the progression of several malignancies, but its role in tumor angiogenesis is unclear. In mice, anti-alpha 6 blocking antibodies reduce tumor angiogenesis, whereas Tiel-dependent alpha 6 gene deletion enhances neovessel formation in melanoma and lung carcinoma. To clarify the discrepancy in these results we used the cre-lox system to generate a mouse line, alpha 6fl/fl-Tie2Cre(+), with alpha 6 gene deletion specifically in Tie2-lineage cells: endothelial cells, pericytes, subsets of hematopoietic stem cells, and Tie2-expressing monocytes/macrophages (TEMs), known for their proangiogenic properties. Loss of alpha 6 expression in alpha 6fl/fl-Tie2Cre+ mice reduced tumor growth in a murine B16F10 melanoma model. Immunohistological analysis of the tumors showed that Tie2-dependent alpha 6 gene deletion was associated with reduced tumor vascularization and with reduced infiltration of proangiogenic Tie2-expressing macrophages. These findings demonstrate that alpha 6 integrin subunit plays a major role in tumor angiogenesis and TEM infiltration. Targeting alpha 6 could be used as a strategy to reduce tumor growth.