CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration
CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration
复制标题
DOI：
10.1593/neo.07307
复制
发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Pienta, Kenneth J.
中科院分区：
文献类型：
--
作者：
Loberg, Robert D.;Ying, Chi;Pienta, Kenneth J.
CCL2影响前列腺癌肿瘤发生和转移的能力可能通过两种不同的机制发生：1）对肿瘤细胞生长和功能的直接影响，2）通过调节巨噬细胞动员和浸润到肿瘤床来间接影响肿瘤微环境。我们之前已经证明，CCL2通过调节前列腺癌上皮细胞的生长、侵袭和迁移对前列腺癌上皮细胞产生直接影响，从而增强肿瘤发生和转移。在这里，我们描述了 CCL2 通过调节单核细胞/巨噬细胞浸润到肿瘤微环境并刺激这些免疫细胞内的表型变化以促进肿瘤生长（肿瘤相关巨噬细胞）对前列腺癌生长和转移的间接影响。将VCaP前列腺癌细胞皮下注射到雄性SCID小鼠中，并监测肿瘤体积、CD68(+)巨噬细胞浸润和微血管密度。全身给予抗CCL2中和抗体（CNTO888和C1142）可显着延缓肿瘤生长并减弱CD68（+）巨噬细胞浸润，同时微血管密度显着降低。这些数据表明，CCL2 通过调节巨噬细胞浸润和增强肿瘤内的血管生成来促进前列腺癌的生长。
The ability of CCL2 to influence prostate cancer tumorigenesis and metastasis may occur through two distinct mechanisms: 1) a direct effect on tumor cell growth and function, and 2) an indirect effect on the tumor microenvironment by the regulation of macrophage mobilization and infiltration into the tumor bed. We have previously demonstrated that CCL2 exerts a direct effect on prostate cancer epithelial cells by the regulation of their growth, invasion, and migration, resulting in enhanced tumorigenesis and metastasis. Here we describe an indirect effect of CCL2 on prostate cancer growth and metastasis by regulating monocyte/ macrophage infiltration into the tumor microenvironment and by stimulating a phenotypic change within these immune cells to promote tumor growth (tumor-associated macrophages). VCaP prostate cancer cells were subcutaneously injected in male SCID mice and monitored for tumor volume, CD68(+) macrophage infiltration, and microvascular density. Systemic administration of antiCCL2 neutralizing antibodies (CNTO888 and C1142) significantly retarded tumor growth and attenuated CD68(+) macrophage infiltration, which was accompanied by a significant decrease in microvascular density. These data suggest that CCL2 contributes to prostate cancer growth through the regulation of macrophage infiltration and enhanced angiogenesis within the tumor.