title: Tie2-dependent deletion of α6 integrin subunit in mice reduces tumor growth and angiogenesis.
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.
authors.affiliation: INSERM UMR-S765.
authors.forename: Claire
authors.initials: C
authors.lastname: Bouvard
authors.affiliation: INSERM UMR-S765.
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Segaoula
authors.affiliation: Institute of Genetics, Cellular and Molecular Biology, INSERM U964, CNRS UMR 7104, University of Strasbourg, Illkirch, France.
authors.forename: Adèle
authors.initials: A
authors.lastname: De Arcangelis
authors.affiliation: University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Galy-Fauroux
authors.affiliation: University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.affiliation: University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.affiliation: Institute of Genetics, Cellular and Molecular Biology, INSERM U964, CNRS UMR 7104, University of Strasbourg, Illkirch, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Georges-Labouesse
authors.affiliation: University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Helley
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039503:Integrin alpha6 / Q000096:biosynthesis / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D042787:Receptor, TIE-2 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D039503:Integrin alpha6; D042787:Receptor, TIE-2; C079086:Tek protein, mouse