靶向周细胞可减少前列腺癌中的新生血管形成和淋巴管生成。

Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer.

作者信息

Ozerdem Ugur

机构信息

La Jolla Institute for Molecular Medicine, San Diego, California 92121, USA.

出版信息

Prostate. 2006 Feb 15;66(3):294-304. doi: 10.1002/pros.20346.

DOI:10.1002/pros.20346

PMID:16245280

Abstract

BACKGROUND

The walls of capillaries in prostate cancer are composed of endothelial cells, and pericytes. NG2 is a transmembrane proteoglycan on nascent pericytes with a functional role in neovascularization.

METHODS

The anti-angiogenic effect of hydron pellets containing NG2 neutralizing antibody was quantified in intracorneal PC-3 and LNCaP xenografts. TRAMP and TRAMP-C1 tumors grafted in NG2 knockout mice represented intrinsic pericyte targeting. TRAMP and TRAMP-C1 grafts were analyzed with confocal microscope for microvascular density (MVD) and lymphatic vascular density (LVD).

RESULTS

NG2 neutralizing antibody decreased corneal neovascularization in PC3 (P<0.0001), and LNCaP (P=0.0079) xenografts. Mean MVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 71% (P=0.0006) and 63% (P=0.0011) lower than wild type controls, respectively. Mean LVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 73% (P=0.0003) and 84% (P<0.0001) lower than wild type controls, respectively.

CONCLUSIONS

Targeting of pericyte-NG2 decreases neovascularization and lymphangiogenesis in prostate cancer significantly.

摘要

背景

前列腺癌毛细血管壁由内皮细胞和周细胞组成。NG2是新生周细胞上的一种跨膜蛋白聚糖，在新血管形成中起作用。

方法

在角膜内PC-3和LNCaP异种移植模型中，对含NG2中和抗体的氢粒子的抗血管生成作用进行定量分析。移植到NG2基因敲除小鼠体内的TRAMP和TRAMP-C1肿瘤代表了对周细胞的内在靶向作用。用共聚焦显微镜分析TRAMP和TRAMP-C1移植瘤的微血管密度（MVD）和淋巴管密度（LVD）。

结果

NG2中和抗体降低了PC3（P<0.0001）和LNCaP（P=0.0079）异种移植瘤的角膜新生血管形成。NG2基因敲除小鼠中TRAMP和TRAMP-C1肿瘤的平均MVD分别比野生型对照低71%（P=0.0006）和63%（P=0.0011）。NG2基因敲除小鼠中TRAMP和TRAMP-C1肿瘤的平均LVD分别比野生型对照低73%（P=0.0003）和84%（P<0.0001）。