Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis

Sonia L. Hernandez, Debarshi Banerjee, Alejandro Garcia, Thaned Kangsamaksin, Wei Yi Cheng, Dimitris Anastassiou, Yasuhiro Funahashi, Angela Kadenhe-Chiweshe, Carrie J. Shawber, Jan K. Kitajewski, Jessica J. Kandel, Darrell J. Yamashiro

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Anti-angiogenesis is a validated strategy to treat cancer, with efficacy in controlling both primary tumor growth and metastasis. The role of the Notch family of proteins in tumor angiogenesis is still emerging, but recent data suggest that Notch signaling may function in the physiologic response to loss of VEGF signaling, and thus participate in tumor adaptation to VEGF inhibitors. Methods. We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct, which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Results: Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Conclusions: Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.

Original languageEnglish (US)
Article number17
JournalVascular Cell
Volume5
Issue number1
DOIs
StatePublished - Sep 27 2013
Externally publishedYes

Keywords

  • Angiogenesis
  • Bevacizumab
  • Neuroblastoma
  • Notch
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Computer Networks and Communications
  • Cell Biology

Fingerprint Dive into the research topics of 'Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis'. Together they form a unique fingerprint.

Cite this