Positive correlation between PEDF expression levels and macrophage density in the human prostate.
Positive correlation between PEDF expression levels and macrophage density in the human prostate.
复制标题
DOI：
10.1002/pros.22595
复制
发表时间：
2013-04
期刊：
影响因子：
2.8
通讯作者：
Filleur, Stephanie
中科院分区：
文献类型：
--
作者：
Nelius, Thomas;Samathanam, Christina;Martinez-Marin, Dalia;Gaines, Natalie;Stevens, Jessica;Hickson, Johnny;de Riese, Werner;Filleur, Stephanie
在这项研究中，我们研究了PEDF在体外和在人前列腺中对单核/巨噬细胞募集和分化的调节能力。利用Boyden小室，我们评估了PEDF对单核细胞和化学激活的RAW264.7巨噬细胞迁移的影响。采用免疫组织化学方法检测正常组织、前列腺炎组织和前列腺癌组织中PEDF的表达和CD68+巨噬细胞的浸润情况。PEDF的表达和巨噬细胞密度与临床病理参数之间存在相关性。用qRT-PCR、Western blotting和ELISA法对M1和M2分化标志物进行定量。在趋化作用方面，PEDF可诱导单核/巨噬细胞迁移。免疫组织化学显示前列腺炎和前列腺癌组织中巨噬细胞较正常组织明显增多。PEDF在间质和上皮中均有不同程度的表达。与正常组织相比，前列腺癌和前列腺炎组织中PEDF基因的表达均下调。在相关研究中，巨噬细胞密度和PEDF表达分别与前列腺大小呈正相关和负相关。最重要的是，PEDF表达与巨噬细胞密度呈正相关。最后，PEDF刺激小鼠和人巨噬细胞诱导型一氧化氮合酶、白介素12和肿瘤坏死因子α的表达，抑制白介素10和精氨酸酶1的表达，证实其为M1型分化。我们的数据表明，PEDF通过诱导单核/巨噬细胞迁移和分化为M1型细胞而直接作用于单核/巨噬细胞。这些发现提示巨噬细胞可能在PEDF的抗肿瘤特性中发挥作用，并可能支持基于PEDF的抗癌治疗的进一步发展。
In this study, we investigated the capacity of PEDF to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate. Using Boyden chambers, we assessed PEDF effect on the migration of monocytes and chemically-activated RAW264.7 macrophages. Normal, prostatitis and prostate cancer specimens were retrospectively selected and examined by immunohistochemistry for PEDF expression and infiltration of immune CD68+macrophagic cells. PEDF expression and macrophage density were then correlated with each other and clinicopathological parameters. M1 and M2 differentiation markers were quantified by qRT-PCR, western blotting and ELISA. In chemotaxis, PEDF induced the migration of monocytes/macrophages. In immunohistochemistry, macrophages were markedly increased in prostatitis and malignant compared to normal tissues. PEDF was expressed at variable levels in the stroma and epithelium. PEDF mRNA was down-regulated in both prostate cancer and prostatitis compared to normal tissues. In correlation studies, macrophage density and PEDF expression were respectively positively and negatively associated with prostate size. Most importantly, PEDF expression positively correlated with macrophage density. Finally, PEDF stimulated the expression of iNOS, IL12 and TNFα; and inhibited IL10 and arginase 1 in mouse and human macrophages confirming a M1-type differentiation. Our data demonstrate that PEDF acts directly on monocytes/macrophages by inducing their migration and differentiation into M1-type cells. These findings suggest a possible role of macrophages in PEDF anti-tumor properties and may support further development of PEDF-based anti-cancer therapy.
登录
查看更多内容
影响因子：
4.8
作者：
Halin, Sofia;Rudolfsson, Stina Haggstrom;Bergh, Anders
通讯作者：
Bergh, Anders
影响因子：
11.2
作者：
Lu, Yi;Cai, Zhong;Zhang, Jian
通讯作者：
Zhang, Jian
影响因子：
3.5
作者：
Adams, Catherine;McCarthy, Helen O.;Hirst, Davi G.
通讯作者：
Hirst, Davi G.
影响因子：
3.6
作者：
Browne, Marybeth;Stellmach, Veronica;Crawford, Susan E.
通讯作者：
Crawford, Susan E.
影响因子：
3.5
作者：
Coulter, Jonathan A.;Page, Natalie L.;McCarthy, Helen O.
通讯作者：
McCarthy, Helen O.