Endoglin interacts with VEGFR2 to promote angiogenesis

Hongyu Tian, Jennifer J. Huang, Christelle Golzio, Xia Gao, Melissa Hector-Greene, Elias Nicholas Katsanis, Gerard C. Blobe*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Endoglin, a TGF-b coreceptor predominantly expressed in endothelial cells, plays an important role in vascular development and tumor-Associated angiogenesis. However, the mechanism by which endoglin regulates angiogenesis, especially during tip cell formation, remains largely unknown. In this study, we report that endoglin promotedVEGF-induced tip cell formation.Mechanistically, endoglin interactedwithVEGF receptor (VEGFR)-2 in a VEGF-dependent manner, which sustained VEGFR2 on the cell surface and prevented its degradation. Endoglin mutants deficient in the ability to interactwithVEGFR2 failedto sustainVEGFR2 on the cell surface and topromote VEGF-induced tip cell formation. Further, an endoglin-Targeting monoclonal antibody (mAb), TRC105, cooperated with aVEGF-A targeting mAb, bevacizumab, to inhibitVEGF signaling and tip cell formation in vitro and to inhibit tumor growth, metastasis, and tumor-Associated angiogenesis in a murine tumor model. This study demonstrate a novelmechanism bywhich endoglin initiates and regulatesVEGF-driven angiogenesiswhile providing a rationale for combining anti-VEGF and anti-endoglin therapy in patients with cancer.

Original languageEnglish (US)
Pages (from-to)2934-2949
Number of pages16
JournalFASEB Journal
Volume32
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • Cancer
  • Endothelial
  • Signaling
  • Sprouting
  • VEGF

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Tian, H., Huang, J. J., Golzio, C., Gao, X., Hector-Greene, M., Katsanis, E. N., & Blobe, G. C. (2018). Endoglin interacts with VEGFR2 to promote angiogenesis. FASEB Journal, 32(6), 2934-2949. https://doi.org/10.1096/fj.201700867RR