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

Bouvard,Claire; Segaoula,Zacharie; De Arcangelis,Adèle; Galy-Fauroux,Isabelle; Mauge,Laetitia; Fischer,Anne-Marie; Georges-Labouesse,Elisabeth; Helley,Dominique

doi:10.3892/ijo.2014.2631

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

Authors:
- Claire Bouvard
- Zacharie Segaoula
- Adèle De Arcangelis
- Isabelle Galy-Fauroux
- Laetitia Mauge
- Anne-Marie Fischer
- Elisabeth Georges-Labouesse
- Dominique Helley
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Affiliations: INSERM UMR-S765, Institute of Genetics, Cellular and Molecular Biology, INSERM U964, CNRS UMR 7104, University of Strasbourg, Illkirch, France, University Paris Descartes, Sorbonne Paris Cité, Paris, France
Published online on: September 1, 2014 https://doi.org/10.3892/ijo.2014.2631
Pages: 2058-2064

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Abstract

The α6 integrin subunit (α6) 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-α6 blocking antibodies reduce tumor angiogenesis, whereas Tie1-dependent α6 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, α6fl/fl‑Tie2Cre+, with α6 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 α6 expression in α6fl/fl‑Tie2Cre+ mice reduced tumor growth in a murine B16F10 melanoma model. Immunohistological analysis of the tumors showed that Tie2-dependent α6 gene deletion was associated with reduced tumor vascularization and with reduced infiltration of proangiogenic Tie2-expressing macrophages. These findings demonstrate that α6 integrin subunit plays a major role in tumor angiogenesis and TEM infiltration. Targeting α6 could be used as a strategy to reduce tumor growth.

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