Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors

Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors
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DOI:
10.1111/j.1440-1827.2009.02369.x
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发表时间:
2009-05-01
影响因子:
2.2
通讯作者:
Takeya, Motohiro
Takeya, Motohiro
中科院分区:
医学4区
文献类型:
--
作者:
Kawamura, Kyoko;Komohara, Yoshihiro;Takeya, Motohiro

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已知肿瘤相关巨噬细胞(TAM)具有免疫抑制性M2巨噬细胞表型。它们通过产生各种介质促进肿瘤生长、侵袭和转移。巨噬细胞,特别是M2极化的巨噬细胞,优先表达CD 163和CD 204,但很少有研究探讨人类卵巢肿瘤中的巨噬细胞表型。因此,本研究的目的是介绍人类卵巢浆液性和粘液性上皮性肿瘤中巨噬细胞分化的结果。该方法侧重于石蜡包埋的肿瘤样品的免疫染色。几乎所有浸润肿瘤组织的巨噬细胞表达CD 163和CD 204,表明表型向M2巨噬细胞转变。交界性和恶性肿瘤中CD 68阳性巨噬细胞以及CD 163和CD 204阳性巨噬细胞的数量显著高于良性肿瘤。它们与组织学恶性度相关性良好。然后评价巨噬细胞集落刺激因子(也称为集落刺激因子; CSF-1),其是被认为诱导TAM向M2表型转化的细胞因子之一。CSF-1在恶性肿瘤细胞中的表达明显高于良性肿瘤细胞,且与组织学恶性程度相关。这些结果表明,来源于肿瘤组织的CSF-1诱导巨噬细胞向M2表型转变,这被认为是促进肿瘤生长。
Tumor-associated macrophages (TAM) are known to possess the immunosuppressive M2 macrophage phenotype. They contribute to tumor growth, invasion, and metastasis by producing various mediators. Macrophages, especially M2 polarized macrophages, preferentially express CD163 and CD204, but few studies have investigated macrophage phenotypes in human ovarian tumors. The purpose of the present study was therefore to present results on macrophage differentiation in human ovarian serous and mucinous epithelial tumors. The method focused on immunostaining of paraffin-embedded tumor samples. Almost all macrophages infiltrating tumor tissues expressed CD163 and CD204, indicating the phenotypic shift toward M2 macrophage. The numbers of CD68-positive macrophages as well as of CD163- and CD204-positive macrophages in borderline and malignant tumors were significantly higher than in benign tumors. They correlated well with histological gradient of malignancy. Macrophage colony-stimulating factor (also known as colony-stimulating factor; CSF-1), which is one of the cytokines considered to induce TAM to polarize toward an M2 phenotype, was then evaluated. CSF-1 expression in malignant tumor cells was significantly higher than that in benign tumor cells and correlated with histological malignancy. These results suggest that CSF-1 derived from tumor tissues induces macrophages to shift toward the M2 phenotype, which is considered to promote tumor growth.