卵巢癌相关成纤维细胞与卵巢癌淋巴结转移的关系

目的:探讨肿瘤相关成纤维细胞(CAFs)与卵巢癌临床病理学特征特别是淋巴结转移的关系,研究CAFs在卵巢癌淋巴管生成和淋巴管内皮细胞(LEC)增殖迁移中的作用。方法:免疫组化法检测、计算机图像处理软件分析71例卵巢癌组织间质中α-平滑肌肌动蛋白(α-SMA)阳性面积百分比,以此代表卵巢癌CAFs的数量。用D2-40标记淋巴管内皮细胞,检测淋巴管密度(LVD)。EdU标记法和Transwell迁移实验检测与CAFs共培养前后淋巴管内皮细胞增殖和迁移情况。结果:卵巢癌有淋巴结转移组间质中CAFs百分比明显高于无淋巴结转移组(P=0.024),分别为(29.39±4.32)%和(22.56±6.78)%。卵巢癌间质CAFs数量与淋巴管密度呈正相关(r=0.504,P=0.0003)。与卵巢癌成纤维细胞共培养后,淋巴管内皮细胞增殖增多2.8倍(P<0.0001),迁移增多5.2倍(P<0.0001)。结论:卵巢癌间质成纤维细胞可能通过促进淋巴管内皮细胞增殖、迁移和淋巴管生成,参与卵巢癌的进展和淋巴结的转移。

The relationship between ovarian cancer associated fibroblasts and lymph node metastases in ovarian cancer

Objective:To investigate the relationship between the amount of CAFs(cancer-associated fibroblasts) and the lymph node metastases in ovarian cancer and evaluate the role of CAFs in lymphangiogenesis and lymphatic endothelial cells(LEC) proliferation and migration.Methods:Using immunohistochemical method and computer-assisted image analysis,we quantified CAFs in 71 human ovarian cancer using α-SMA as a marker.Lymph vessel density(LVD) was measured by quantitative immunohistochemistry using anti-D2-40 antibody.EdU incorporation assay and Transwell migration assay were conducted to evaluate the proliferation and motility of EOC cell lines cocultured with CAFs.Results:The CAFs in lymph-node positive malignancies was more than that in lymph-node negative malignancies,(29.39±4.32)% and(22.56±6.78)% respectively(P=0.024).The lymphatic vessel density was positively correlated with the number of CAFs and has statistic significance.By co-cultivation with CAFs,the number of dividing or magration LEC increased 2.8-fold(P<0.0001) and 5.2-fold(P<0.0001) respectively.Conclusion:CAFs in ovarian cancer seem to play an important role in the ovarian cancer development and lymph node metastases through induced lymphangiogenesis and LEC proliferation and migration.