Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion.

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State: Public
Version: Final published version
Serval ID
serval:BIB_42D2A2696272
Type
Article: article from journal or magazin.
Collection
Publications
Title
Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion.
Journal
Oncotarget
Author(s)
Alonso F., Domingos-Pereira S., Le Gal L., Derré L., Meda P., Jichlinski P., Nardelli-Haefliger D., Haefliger J.A.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Publication state
Published
Issued date
22/03/2016
Peer-reviewed
Oui
Volume
7
Number
12
Pages
14015-14028
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Endothelial connexin40 (Cx40) contributes to regulate the structure and function of vessels. We have examined whether the protein also modulates the altered growth of vessels in tumor models established in control mice (WT), mice lacking Cx40 (Cx40-/-), and mice expressing the protein solely in endothelial cells (Tie2-Cx40). Tumoral angiogenesis and growth were reduced, whereas vessel perfusion, smooth muscle cell (SMC) coverage and animal survival were increased in Cx40-/- but not Tie2-Cx40 mice, revealing a critical involvement of endothelial Cx40 in transformed tissues independently of the hypertensive status of Cx40-/- mice. As a result, Cx40-/- mice bearing tumors survived significantly longer than corresponding controls, including after a cytotoxic administration. Comparable observations were made in WT mice injected with a peptide targeting Cx40, supporting the Cx40 involvement. This involvement was further confirmed in the absence of Cx40 or by peptide-inhibition of this connexin in aorta-sprouting, matrigel plug and SMC migration assays, and associated with a decreased expression of the phosphorylated form of endothelial nitric oxide synthase. The data identify Cx40 as a potential novel target in cancer treatment.

Keywords
Animals, Aorta/pathology, Apoptosis, Biomarkers, Tumor/metabolism, Blood Vessels/physiology, Cell Proliferation, Connexins/antagonists & inhibitors, Connexins/metabolism, Endothelium, Vascular/metabolism, Endothelium, Vascular/pathology, Female, Humans, Lung Neoplasms/blood supply, Lung Neoplasms/pathology, Lung Neoplasms/prevention & control, Melanoma, Experimental/blood supply, Melanoma, Experimental/pathology, Melanoma, Experimental/prevention & control, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasm Invasiveness, Neovascularization, Pathologic/prevention & control, Perfusion, Tumor Cells, Cultured, Urinary Bladder Neoplasms/blood supply, Urinary Bladder Neoplasms/pathology, Urinary Bladder Neoplasms/prevention & control, angiogenesis, cell-cell communication, connexins, transgenic mice, tumors
Pubmed
Web of science
Open Access
Yes
Create date
27/12/2016 13:35
Last modification date
20/08/2019 14:45
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