Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion
Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion
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DOI：
10.1016/j.canlet.2011.01.011
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发表时间：
2011-04-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
--
作者：
Zhang, Yuan;Tang, Huijuan;Wang, Zehua
癌症相关成纤维细胞（CAF）被认为在癌症的发生和发展中起重要作用。然而，很少有研究已经做了评估CAFs在上皮性卵巢癌（EOC）的发展中的作用。为了解决这个问题，91份标本用α-平滑肌肌动蛋白（α-SMA）和成纤维细胞活化蛋白（FAP）抗体进行免疫染色，以定量CAF，并用抗体D2-40和CD 34评价病变的淋巴管密度（LVD）和微血管密度（MVD）。正常卵巢组织中未见α-SMA和FAP阳性的成纤维细胞。上皮性卵巢癌中CAF的检出率明显高于交界性肿瘤和良性肿瘤（P < 0.01）。EOC中CAF的增多与疾病的晚期（P = 0.002）、淋巴结转移（P = 0.02）和网膜转移（P < 0.0001）以及LVD（P = 0.002）和MVD（P = 0.0004）的增加有关。与正常卵巢组织中分离的成纤维细胞（NF）相比，从EOC组织中分离的CAFs在体外诱导更多的癌细胞侵袭（P = 0.003）和迁移（P = 0.005）。我们的数据表明CAFs在卵巢癌的进展和转移中起着至关重要的作用。靶向CAFs作为卵巢癌的治疗策略是一个有趣的概念，需要进一步研究。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Cancer-associated fibroblasts (CAFs) are thought to play an essential role in cancer initiation and development. However, little research has been done to evaluate the role of CAFs in epithelial ovarian cancer (EOC) development. To address this issue, ninety-one specimens were immunostained with alpha-smooth muscle actin (alpha-SMA) and fibroblast activation protein (FAP) antibodies to quantify CAFs, and antibodies D2-40 and CD34 to evaluate the lymphatic vessel density (LVD) and microvessel density (MVD) of the lesions. We found there were no alpha-SMA or FAP positive fibroblasts in normal ovary tissues. More CAFs were found in EOC than in borderline tumors and benign tumors (P < 0.01). Abundant CAFs in EOC were associated with advanced-stage disease (P = 0.002), the occurrence of lymph node metastases (P = 0.02) and omentum metastases (P < 0.0001), and increased LVD (P = 0.002) and MVD (P = 0.0004). CAFs isolated from EOC tissues induced more cancer cells to invade (P = 0.003) and migrate (P = 0.005) compared with normal fibroblasts (NFs) isolated from normal ovary tissues in vitro. Our data indicate that CAFs play a vital role in ovarian cancer progression and metastasis. Targeting CAFs as a therapeutic strategy against ovarian cancer is an intriguing concept that needs further study. (C) 2011 Elsevier Ireland Ltd. All rights reserved.