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Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination

In English

Författare

  • Charlotte Anderberg
  • Sara I. Cunha
  • Zhenhua Zhai
  • Eliane Cortez
  • Evangelia Pardali
  • Jill R. Johnson
  • Marcela Franco
  • Marta Paez-Ribes
  • Ross Cordiner
  • Jonas Fuxe
  • Bengt R. Johansson
  • Marie-Jose Goumans
  • Oriol Casanovas
  • Peter ten Dijke
  • Helen M. Arthur
  • Kristian Pietras
Visa allt

Summary, in English

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-beta 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.

Avdelning/ar

Publiceringsår

2013

Språk

Engelska

Sidor

563-579

Publikation/Tidskrift/Serie

Journal of Experimental Medicine

Volym

210

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Rockefeller University Press

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Experimental oncology

ISBN/ISSN/Övrigt

  • ISSN: 1540-9538