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

Vascular Cell

Darrell J Yamashiro⁵  Jessica J Kandel³  Jan K Kitajewski⁵  Carrie J Shawber²  Angela Kadenhe-Chiweshe³  Yasuhiro Funahashi²  Dimitris Anastassiou¹  Wei-Yi Cheng¹  Thaned Kangsamaksin²  Alejandro Garcia³  Debarshi Banerjee⁴  Sonia L Hernandez⁴ 

[1] Center for Computational Biology and Bioinformatics, Columbia University, New York, NY, USA;Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA;Department of Surgery, Columbia University Medical Center, New York, NY, USA;Department of Pediatrics, Columbia University Medical Center, New York, NY, USA;Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA

关键词: Bevacizumab;    Angiogenesis;    Notch;    Vascular endothelial growth factor;    Neuroblastoma;   

Others  :  801587
DOI  :  10.1186/2045-824X-5-17

 received in 2013-05-03, accepted in 2013-09-20,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Hernandez et al.; licensee BioMed Central Ltd.

【 图 表 】

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