Deleted in malignant brain tumors 1 is present in the vascular extracellular matrix and promotes angiogenesis

Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):442-8. doi: 10.1161/ATVBAHA.111.239830. Epub 2011 Nov 3.


Objective: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells.

Methods and results: DMBT1 was secreted into the extracellular matrix (ECM) by endothelial cells in vitro and in situ and the presence of DMBT1 in the ECM increased endothelial cell adherence. Endothelial cell-derived DMBT1 associated with galectin-3 (coprecipitation), and human recombinant DMBT1 bound EGF, vascular endothelial growth factor and Delta-like (Dll) 4 (specific ELISAs). Compared to cells from wild-type mice, endothelial cells from DMBT1(-/-) mice demonstrated reduced migration, proliferation, and tube formation. In vivo recovery from hindlimb ischemia was attenuated in DMBT1(-/-) animals as was vascular endothelial growth factor -induced endothelial sprouting from isolated aortic rings; the latter response could be rescued by the addition of recombinant DMBT1. The Notch pathway is involved in multiple aspects of vascular development, including arterial-venous differentiation and we found that endothelial cells from DMBT1(-/-) mice expressed more EphrinB2 than cells from wild-type mice. Levels of Dll1, Dll4, Hes1, Hey1, and EphB4, on the other hand, were decreased.

Conclusions: Taken together, the results of this study indicate that DMBT1 functions as an important endothelium-derived ECM protein that is able to bind angiogenic factors and promote adhesion, migration, proliferation, and angiogenesis as well as vascular repair. Mechanistically, DMBT1 interacts with galectin-3 and modulates the Notch signaling pathway as well as the differential expression of ephrin-B2 and EphB4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • DNA-Binding Proteins
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Extracellular Matrix / metabolism*
  • Galectin 3 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Mucins / deficiency
  • Mucins / genetics
  • Mucins / metabolism*
  • Neovascularization, Physiologic / physiology*
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology
  • Tumor Suppressor Proteins


  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Dmbt1 protein, mouse
  • Galectin 3
  • Mucins
  • Receptors, Notch
  • Tumor Suppressor Proteins