Overexpression of Notch ligand Dll1 in B16 melanoma cells leads to reduced tumor growth due to attenuated vascularization

Cancer Lett. 2011 Oct 28;309(2):220-7. doi: 10.1016/j.canlet.2011.06.008. Epub 2011 Jun 24.

Abstract

Notch signaling plays an important role in vascular development and tumor angiogenesis. It has been shown that disruption of Dll4-triggered Notch signal activation effectively inhibits tumor growth, but this treatment also results in the formation of vascular neoplasms. In this study, we investigate the effects of over-expressing Notch ligand Dll1 in B16 melanoma cells on tumor cell proliferation and tumor growth in vitro and in vivo. Our results showed that over-expression of Dll1 could activate Notch signaling in tumor cells, and promote tumor cell proliferation in vitro. In contrast, growth of Dll1-over-expressing tumors in vivo was reduced, due to abnormal tumor vessel formation. Impaired tumor vasculature enhanced hypoxia and necrosis in tumor tissues, leading to retarded tumor growth. These results suggest that activation of Notch signaling may serve as an anti-angiogenesis strategy in the treatment of malignant tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Melanoma, Experimental / blood supply*
  • Melanoma, Experimental / pathology
  • Mice
  • Necrosis
  • Neovascularization, Pathologic*
  • Receptor, Notch1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Skin Neoplasms
  • Vascular Endothelial Growth Factor A

Substances

  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Vascular Endothelial Growth Factor A