Differential expression of angiopoietin-2 and vascular endothelial growth factor in androgen-independent prostate cancer models

BJU Int. 2008 Sep;102(8):1034-9. doi: 10.1111/j.1464-410X.2008.07768.x. Epub 2008 May 16.

Abstract

Objective: To investigate the relationship between microvessel density (MVD), blood vessel morphology and the expression of angiopoietin (Ang)-1, Ang-2, tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Tie)-2, and vascular endothelial growth factor (VEGF) in androgen-dependent (AD) and androgen-independent (AI) prostate cancer models, to gain insight into the regulation of angiogenesis at different stages of prostate cancer.

Materials and methods: MVD and blood vessel morphology were evaluated by CD34 immunohistochemical staining. The mRNA and protein secretion of the Angs, Tie-2 and VEGF were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively, in LNCaP (AD) and LNCaP-19, C4-2, C4-2B4 and PC-3 (AI) prostate cancer xenografts in mice.

Results: LNCaP, C4-2 and C4-2B4 xenografts had high expression of Ang-2 and VEGF, similar MVD and blood vessel morphology. However, the most angiogenic cell line LNCaP-19 expressed low levels of both factors and had different vessel morphology. PC-3 xenografts had a similar MVD to LNCaP, C4-2 and C4-2B4, but the Ang-2 and VEGF expression as well as the vessel morphology were similar to LNCaP-19.

Conclusion: The differences in MVD, blood vessel morphology and the expression of Ang-2 and VEGF show that prostate cancer cells display angiogenic heterogeneity, which indicates different roles of these factors in the regulation of angiogenesis in different stages of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism
  • Angiopoietin-1 / metabolism
  • Angiopoietin-2 / metabolism*
  • Animals
  • Biomarkers, Tumor / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms, Hormone-Dependent / blood supply*
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Prostatic Neoplasms / blood supply*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Androgens
  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A