肿瘤相关M2型巨噬细胞在卵巢癌组织中的分布及意义

Distribution and clinical significance of M2-type macrophages in ovarian cancer tissues

目的探讨卵巢癌组织中M2型巨噬细胞的分布及其对卵巢癌侵袭转移相关基质金属蛋白酶(MMPs)表达的影响。方法免疫组织化学法检测上皮性卵巢癌(34例)、交界性卵巢肿瘤(16例)和卵巢良性肿瘤(18例)组织切片中CD68、CD206和MMP-9的表达,比较卵巢癌样本中阳性表达细胞数与患者年龄、病理类型、FIGO分期、组织学分化和淋巴结转移的关系。并利用流式细胞术比较其中12例上皮性卵巢癌和11例卵巢良性肿瘤新鲜组织中CD68+~CD206+~细胞比例。实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印记(Western blot)方法分别评价卵巢癌和卵巢良性肿瘤组织内MMP-2、MMP-9和MMP-10水平。结果卵巢癌组织中CD68+~、CD206+~和MMP-9+~细胞数量明显高于交界性卵巢肿瘤和卵巢良性肿瘤组织(P<0.05),卵巢癌组织中CD68+~、CD206+~和MMP-9+~细胞数与患者FIGO分期和淋巴结转移均有统计学关系(P<0.05)。卵巢癌组织中CD68+~和CD206+~细胞数量呈正相关关系(r=0.508,P<0.05),且MMP-9+~与CD68+~和CD206+~细胞数量也分别呈正相关(r=0.611,P<0.001;r=0.744,P<0.001)。卵巢癌新鲜组织中CD68+~CD206+~细胞比例明显高于良性卵巢肿瘤(P<0.05),且卵巢癌组织MMP-2、MMP-9和MMP-10 m RNA和蛋白表达水平较卵巢良性肿瘤具有统计学意义(P<0.05)。结论卵巢癌组织中具有较高水平的M2型巨噬细胞,与卵巢癌侵袭转移和临床进展有重要的联系。

This study performed to investigate the distribution of M2-type macrophages in ovarian cancertissues and its influence on the expression of matrix metalloproteinases（MMPs）,which relates to the invasion andmetastasis of ovarian cancer.Immunohistochemistry method was applied to detect the expression of CD68,CD206 and MMP-9 in epithelial ovarian cancer（n=34）,borderline ovarian tumor（n=16） and benign ovarian tumor（n=18）.We also analyzed the relationship of the positive cells number with age,pathological type,FIGO stage,histologicdifferentiation and lymphatic invasion of patients with ovarian cancer.Flow cytometry was used to investigate theproportion of CD68＋~CD206＋~cells in epithelial ovarian cancer（n=12） and benign ovarian tumor（n=11）;real-timePCR and Western blot were utilized to evaluate the levels of MMP-2,MMP-9 and MMP-10 in ovarian cancer andbenign ovarian tumors.We found that the percentages of CD68＋~,CD206＋~and MMP-9＋~cells were significantly higherin ova＋~rian cancer,as compared with borderline ovarian tumor and benign ovarian tumor（P〈0.05）.The number ofCD68,CD206＋~or MMP-9＋~cells in ovarian cancer tissues was significantly related to FIGO stage and lymphaticinvasion＋^（P〈0.05）.The Spearman correlation analysis showed that the distributions of CD68＋~macrophages andCD206 macrophages in ovarian cancer were strongly correlated（r=0.508,P〈0.05）.The number of infiltrating CD68＋~and CD206＋~macrophages was significantly correlatedwith the number of MMP-9＋~cells（r=0.611,P〈0.05 and r=0.744,P〈0.05 respectively）.It was alsodetected that the percentage of CD68＋~CD206＋~cellswas significantly higher in ovarian cancer incomparison with that of benign ovarian tumor（P〈0.05）.The m RNA and protein expression levels of MMP-2,MMP-9 and MMP-10 were significantly higher inovarian cancer than those in benign ovarian tumor.In conclusion,there are abundant M2-type macrophagesinfiltrated in ovarian cancer tissues,which may associate with the metastasis and poor outcome of patients withovarian cancer.Epithelial ovarian cancer;Matrix metalloproteinases;M2-type macrophages.