癌相关纤维母细胞对卵巢癌细胞的侵袭和转移的作用

Effects of cancer-assocaited fibroblasts on migration and metastasis of ovarian cancers

目的 探讨癌相关纤维母细胞(CAF)对卵巢癌细胞侵袭和转移作用,为卵巢癌的合理有效治疗提供新的思路和作用靶点。方法 采用免疫组化方法检测60例卵巢癌组织和20例正常卵巢组织中平滑肌肌动蛋白(α-SMA)、纤维母细胞活化蛋白(FAP-α)、CD34和D2-40的表达情况,其中α-SMA和FAP-α用来标记CAF,CD34标记微血管密度(MVD),D2-40标记淋巴管密度(LVD),分析α-SMA、FAP-α、CD34和D2-40表达改变与卵巢癌患者临床病理特征的关系。结果 正常卵巢组织中,α-SMA和FAP-α均为阴性表达,α-SMA、FAP-α表达于卵巢癌相关纤维母细胞质中,并且与分化程度、FIGO分期、侵袭深度、淋巴结转移、淋巴管密度增加和微血管密度增加相关(P<0.05),而与患者的年龄、组织学分型无关(P>0.05)。MVD与分化程度、FIGO分期、侵袭深度和淋巴结转移相关(P<0.05),而与年龄无关(P>0.05)。LVD与分化程度、FIGO分期、侵袭深度和淋巴结转移相关(P<0.05),而与年龄无关(P>0.05)。α-SMA和FAP-α表达与MVD和LVD正相关(P<0.05)。结论 CAF通过促进血管再生和淋巴管再生而促进卵巢癌细胞的侵袭和转移,未来可能成为卵巢癌治疗的新靶点。

Objective To investigate the effects of cancer-associated fibroblasts(CAFs) on the invasion and metastasis of human ovarian cancer to provide new ideas and targets for the rational and effective treatment of ovarian cancer. Methods Eighty specimens(sixty ovarian cancer and twenty normal ovarian tissues) were immunostained with α-smooth muscle actin(α-SMA) and fibroblast activation protein(FAP-α) to quantify ovarian cancer-associated fibroblasts, and CD34 and D2-40 were used to evaluate the microvessel density(MVD) and lymphatic vessel density(LVD) of the lesions. The relationship of their expression alterations with clinicopathological features was analyzed. Results SMA and FAP-α were negative in normal ovarian tissues, both of them were positive in ovarian cancer. The expression of α-SMA and FAP-α in ovarian cancer was related to differentiation degree, FIGO stage, depth of tumor invasion, lymph node metastasis, and increased LVD and MVD(P<0.05), but not related to ages and histologic types(P>0.05). MVD in ovarian cancer was related to differentiation degree, FIGO stage, depth of tumor invasion, lymph node metastasis(P<0.05), but not related to ages(P>0.05). LVD in ovarian cancer was related to differentiation degree, FIGO stage, depth of tumor invasion, lymph node metastasis(P<0.05), but not related to ages(P>0.05). The expression of α-SMA and FAP-α was positively correlated to MVD and LVD in ovarian carcinoma. Conclusion CAFs play a vital role in ovarian cancer invasion and metastasis by promoting angiogenesis and lymphangiogenesis. CAFs may become a new target for ovarian cancer treatment in the future.