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.