alexa Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide.
Medicine

Medicine

Translational Medicine

Author(s): Brouet A, DeWever J, Martinive P, Havaux X, Bouzin C,

Abstract Share this page

Abstract In tumors, caveolin-1, the structural protein of caveolae, constitutes a key switch through its function as a tumor suppressor and a promoter of metastases. In endothelial cells (EC), caveolin is also known to directly interact with the endothelial nitric oxide synthase (eNOS) and thereby to modulate nitric oxide (NO)-mediated processes including vasodilation and angiogenesis. In this study, we examined whether the modulation of the stoichiometry of the caveolin/eNOS complex in EC lining tumor blood vessels could affect the tumor vasculature and consecutively tumor growth. For this purpose, we used cationic lipids, which are delivery systems effective at targeting tumor vs. normal vascular networks. We first documented that in vitro caveolin transfection led to the inhibition of both VEGF-induced EC migration and tube formation on Matrigel. The DNA-lipocomplex was then administered through the tail vein of tumor-bearing mice. The direct interaction between recombinant caveolin and native eNOS was validated in coimmunoprecipitation experiments from tumor extracts. A dramatic tumor growth delay was observed in mice transfected with caveolin- vs. sham-transfected animals. Using laser Doppler imaging and microprobes, we found that in the early time after lipofection (e.g., when macroscopic effects on the integrity of the tumor vasculature were not detectable), caveolin expression impaired NO-dependent tumor blood flow. At later stages post-transfection, a decrease in tumor microvessel density in the central core of caveolin-transfected tumors was also documented. In conclusion, our study reveals that by exploiting the exquisite regulatory interaction between eNOS and caveolin and the propensity of cationic lipids to target EC lining tumor blood vessels, caveolin plasmid delivery appears to be a safe and efficient way to block neoangiogenesis and vascular function in solid tumors, independently of any direct effects on tumor cells. This article was published in FASEB J and referenced in Translational Medicine

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords