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

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.