Notch4 is required for tumor onset and perfusion

Journal of Angiogenesis Research

Rong A Wang³  Christin A Cvetic³  Thomas Gridley²  Olivera Marjanovic⁷  Ellen Cheang⁴  Seth K Bechis⁵  Ruchika Srinivasan⁶  Henar Cuervo³  Xiaoqing Wu¹  Maria José Costa⁸ 

[1] Present address: Tech Data Services, LLC, King of Prussia, PA19406, USA;Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA;Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA;Present address: Department of Radiology, University of California Davis Medical Center, Sacramento, CA 95817, USA;Present address: Department of Urology, Massachusetts General Hospital, Boston, MA 02114, USA;Present address: Novartis Healthcare Pvt. Ltd., Hyderabad, India;Present address: School of Public; Division of Infectious Diseases and Vaccinology, University of California Davis Medical Center, Sacramento, CA 95817, USA;Present address: Department of Pediatrics and Program in Regenerative Medicine, Stanford University, Stanford, CA 94305, USA

关键词: Perfusion;    Blood vessel;    Tumor;    Angiogenesis;    Notch;   

Others  :  801676
DOI  :  10.1186/2045-824X-5-7

 received in 2013-02-19, accepted in 2013-04-05,  发布年份 2013

【 摘 要 】

Background

Notch4 is a member of the Notch family of receptors that is primarily expressed in the vascular endothelial cells. Genetic deletion of Notch4 does not result in an overt phenotype in mice, thus the function of Notch4 remains poorly understood.

Methods

We examined the requirement for Notch4 in the development of breast cancer vasculature. Orthotopic transplantation of mouse mammary tumor cells wild type for Notch4 into Notch4 deficient hosts enabled us to delineate the contribution of host Notch4 independent of its function in the tumor cell compartment.

Results

Here, we show that Notch4 expression is required for tumor onset and early tumor perfusion in a mouse model of breast cancer. We found that Notch4 expression is upregulated in mouse and human mammary tumor vasculature. Moreover, host Notch4 deficiency delayed the onset of MMTV-PyMT tumors, wild type for Notch4, after transplantation. Vessel perfusion was decreased in tumors established in Notch4-deficient hosts. Unlike in inhibition of Notch1 or Dll4, vessel density and branching in tumors developed in Notch4-deficient mice were unchanged. However, final tumor size was similar between tumors grown in wild type and Notch4 null hosts.

Conclusion

Our results suggest a novel role for Notch4 in the establishment of tumor colonies and vessel perfusion of transplanted mammary tumors.

【 授权许可】

   
2013 Costa et al.; licensee BioMed Central Ltd.

【 图 表 】

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