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.

journal_name

Int J Oncol

authors

Bouvard C,Segaoula Z,De Arcangelis A,Galy-Fauroux I,Mauge L,Fischer AM,Georges-Labouesse E,Helley D

doi

10.3892/ijo.2014.2631

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

2058-64

issue

5

eissn

1019-6439

issn

1791-2423

journal_volume

45

pub_type

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