Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells

Br J Cancer. 2012 Mar 13;106(6):1214-23. doi: 10.1038/bjc.2012.59. Epub 2012 Feb 28.

Abstract

Background: We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs.

Methods: The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients.

Results: Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers.

Conclusion: These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Autocrine Communication
  • Biglycan / blood
  • Biglycan / genetics
  • Biglycan / metabolism*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / blood supply
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Endothelial Cells / metabolism*
  • Endothelial Cells / physiology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Gene Knockdown Techniques
  • Humans
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / blood supply
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Melanoma / blood supply
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation

Substances

  • Antigens, CD
  • BGN protein, human
  • Biglycan
  • Biomarkers, Tumor