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 Oncoljournal_title
International journal of oncologyauthors
Bouvard C,Segaoula Z,De Arcangelis A,Galy-Fauroux I,Mauge L,Fischer AM,Georges-Labouesse E,Helley Ddoi
10.3892/ijo.2014.2631subject
Has Abstractpub_date
2014-11-01 00:00:00pages
2058-64issue
5eissn
1019-6439issn
1791-2423journal_volume
45pub_type
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journal_title:International journal of oncology
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