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.


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.


CONCLUSIONS
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.
Tesan
Tajana
T
Department of Urology, Lundberg Laboratory for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Gustavsson
Heléne
H
Welén
Karin
K
Damber
Jan-Erik
JE
D000728:Androgens / Q000378:metabolism; D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000728:Androgens; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A