alexa An intact overexpressed E-cadherin alpha,beta-catenin axis characterizes the lymphovascular emboli of inflammatory breast carcinoma.
Oncology

Oncology

Journal of Cancer Science & Therapy

Author(s): Tomlinson JS, Alpaugh ML, Barsky SH

Abstract Share this page

Abstract The step of intravasation (lymphovascular invasion), a rate-limiting step in metastasis, is greatly exaggerated in inflammatory breast carcinoma (IBC). Because nearly all human breast carcinoma cell lines grow as solitary nodules in nude/severe combined immunodeficient mice without manifesting lymphovascular invasion, this step has been difficult to study. We captured the essence of the IBC phenotype by establishing a unique human transplantable IBC xenograft, MARY-X, which manifests florid lymphovascular emboli in severe combined immunodeficient/nude mice. Comparing MARY-X with common non-IBC cell lines/xenografts, we discovered an overexpressed and overfunctioning E-cadherin/alpha,beta-catenin axis. In MARY-X, the E-cadherin and catenins were part of a structurally and functionally intact adhesion axis involving the actin cytoskeleton. In vitro, MARY-X grew as round compact spheroids with a cell density 5-10-fold higher than that of other lines. The spheroids of MARY-X completely disadhered when placed in media containing absent Ca(2+) or anti-E-cadherin antibodies or when retrovirally transfected with a dominant-negative E-cadherin mutant (H-2K(d)-E-cad). Anti-E-cadherin antibodies injected i.v. immunolocalized to the pulmonary lymphovascular emboli of MARY-X and caused their dissolution. H-2K(d)-E-cad-transfected MARY-X spheroids were only weakly tumorigenic and did not form lymphovascular emboli. A total of 90\% of human IBCs showed increased membrane E-cadherin/alpha,beta-catenin immunoreactivity. These findings indicate that it is the gain and not the loss of the E-cadherin axis that contributes to the IBC phenotype.
This article was published in Cancer Res and referenced in Journal of Cancer Science & Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

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

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