The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

Compound genetically engineered mouse models of cancer reveal dual targeting of ALK1 and endoglin as a synergistic opportunity to impinge on angiogenic TGF-β signaling

Author

  • Nikolas M. Eleftheriou
  • Jonas Sjölund
  • Matteo Bocci
  • Eliane Cortez
  • Se Jin Lee
  • Sara I. Cunha
  • Kristian Pietras

Summary, in English

Angiogenesis occurs early in tumor development, sustains primary tumor growth and provides a route for metastatic escape. The TGF-β family receptors modulate angiogenesis via endothelial-cell specific pathways. Here we investigate the interaction of two such receptors, ALK1 and endoglin, in pancreatic neuroendocrine tumors (PanNET). Independently, ALK1 and endoglin deficiencies exhibited genetically divergent phenotypes, while both highly correlate to an endothelial metagene in human and mouse PanNETs. A concurrent deficiency of both receptors synergistically decreased tumor burden to a greater extent than either individual knockdown. Furthermore, the knockout of Gdf2 (BMP9), the primary ligand for ALK1 and endoglin, exhibited a mixed phenotype from each of ALK1 and endoglin deficiencies; overall primary tumor burden decreased, but hepatic metastases increased. Tumors lacking BMP9 display a hyperbranching vasculature, and an increase in vascular mesenchymal-marker expression, which may be implicit in the increase in metastases. Taken together, our work cautions against singular blockade of BMP9 and instead demonstrates the utility of dual blockade of ALK1 and endoglin as a strategy for antiangiogenic therapy in PanNET.

Department/s

  • Division of Translational Cancer Research
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2016

Language

English

Pages

84314-84325

Publication/Series

Oncotarget

Volume

7

Issue

51

Document type

Journal article

Publisher

Impact Journals

Topic

  • Cell and Molecular Biology
  • Medical Genetics
  • Immunology in the medical area

Keywords

  • ALK1
  • Angiogenesis
  • BMP9
  • Endoglin
  • Targeted therapy

Status

Published

ISBN/ISSN/Other

  • ISSN: 1949-2553