Browse by author
Lookup NU author(s): Dr Jason Zhai, Ross Cordiner, Professor Helen ArthurORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. We investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-β in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response, and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition, a process of previously unknown significance in cancer biology, but shown by us to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF (vascular endothelial growth factor) agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer.
Author(s): Anderberg C, Cunha S, Zhai Z, Cortez E, Pardali E, Johnson J, Franco M, Paez-Ribes M, Cordiner R, Fuxe J, Johansson BR, Goumans MJ, Casanovas O, ten Dijke P, Arthur HM, Pietras K
Publication type: Article
Publication status: Published
Journal: Journal of Experimental Medicine
Year: 2013
Volume: 210
Issue: 3
Pages: 563-579
Print publication date: 11/02/2013
ISSN (print): 0022-1007
ISSN (electronic): 1540-9538
Publisher: Rockefeller University Press
URL: http://dx.doi.org/10.1084/jem.20120662
DOI: 10.1084/jem.20120662
Altmetrics provided by Altmetric
