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血管生成素-2和血管内皮生长因子在雄激素非依赖性前列腺癌模型中的差异表达

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

作者信息

Tesan Tajana, Gustavsson Heléne, Welén Karin, Damber Jan-Erik

机构信息

Department of Urology, Lundberg Laboratory for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.

出版信息

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.

摘要

目的

研究雄激素依赖型(AD)和雄激素非依赖型(AI)前列腺癌模型中微血管密度(MVD)、血管形态与血管生成素(Ang)-1、Ang-2、具有免疫球蛋白和表皮生长因子同源结构域的酪氨酸激酶(Tie)-2以及血管内皮生长因子(VEGF)表达之间的关系,以深入了解前列腺癌不同阶段血管生成的调控机制。

材料与方法

采用CD34免疫组织化学染色评估MVD和血管形态。分别通过实时聚合酶链反应和酶联免疫吸附测定法,检测小鼠体内LNCaP(AD)和LNCaP-19、C4-2、C4-2B4及PC-3(AI)前列腺癌异种移植瘤中Angs、Tie-2和VEGF的mRNA及蛋白分泌情况。

结果

LNCaP、C4-2和C4-2B4异种移植瘤中Ang-2和VEGF表达较高,MVD和血管形态相似。然而,血管生成能力最强的细胞系LNCaP-19中这两种因子表达水平较低,且血管形态不同。PC-3异种移植瘤的MVD与LNCaP、C4-2和C4-2B4相似,但Ang-2和VEGF表达以及血管形态与LNCaP-19相似。

结论

MVD、血管形态以及Ang-2和VEGF表达的差异表明,前列腺癌细胞表现出血管生成异质性,这表明这些因子在前列腺癌不同阶段的血管生成调控中发挥着不同作用。

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