title: Notch4 is required for tumor onset and perfusion.
abstract: 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.
  
  
  CONCLUSIONS
  Our results suggest a novel role for Notch4 in the establishment of tumor colonies and vessel perfusion of transplanted mammary tumors.
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.|Present address: Department of Pediatrics and Program in Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Costa
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.|Present address: Tech Data Services, LLC, King of Prussia, PA19406, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.
authors.forename: Henar
authors.initials: H
authors.lastname: Cuervo
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.|Present address: Novartis Healthcare Pvt. Ltd., Hyderabad, India.
authors.forename: Ruchika
authors.initials: R
authors.lastname: Srinivasan
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.|Present address: Department of Urology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Seth K
authors.initials: SK
authors.lastname: Bechis
authors.affiliation: 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.
authors.forename: Ellen
authors.initials: E
authors.lastname: Cheang
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.|Present address: School of Public; Division of Infectious Diseases and Vaccinology, University of California Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Olivera
authors.initials: O
authors.lastname: Marjanovic
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.
authors.forename: Christin A
authors.initials: CA
authors.lastname: Cvetic
authors.affiliation: Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.
authors.forename: Rong A
authors.initials: RA
authors.lastname: Wang