Tumor cell-fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer
Tumor cell-fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer
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DOI：
10.3892/ijmm.2019.4361
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发表时间：
2019-12-01
影响因子：
5.4
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
--
作者：
Han, Qing;Huang, Bangxing;Wang, Zehua
腹水多细胞聚集体(MCAS)促进卵巢癌腹膜转移。本研究旨在阐明肿瘤相关成纤维细胞(CAF)在高级别浆液性卵巢癌(HGSOC)MCA形成和转移中的作用。免疫组织化学方法检测腹水MCAS的细胞表型和CAF的存在。悬液共培养法检测CAF在肿瘤细胞MCA形成中的作用。用原代腹水肿瘤细胞和大网膜CAF悬液培养产生MCAS，通过体外和体内间皮细胞清除和黏附实验评价MCAS的侵袭性。腹水中可见含有CAF的MCAS和肿瘤细胞。CAFS促进肿瘤细胞聚集和致密形成MCAS，增强肿瘤细胞间皮细胞的清除和黏附能力。这些发现表明，腹水CAF通过与肿瘤细胞形成异型聚集体促进腹膜转移，它们可能成为治疗HGSOC的潜在靶点。
Ascitic multicellular aggregates (MCAs) promote peritoneal metastasis of ovarian cancer. The aim of the present study was to elucidate the role of cancer-associated fibroblasts (CAFs) in MCA formation and metastasis in patients with high-grade serous ovarian cancer (HGSOC). Immunohistochemistry was used to identify the cell phenotypes and the presence of CAFs in ascitic MCAs. The role of CAFs in tumor-cell MCA formation was assessed by co-culture in suspension. Primary ascitic tumor cells and omental CAFs were used to generate ex vivo MCAs in hanging drops, and the invasiveness of MCAs was evaluated by mesothelial clearance and adhesion assays in vitro and in vivo. MCAs containing CAFs and tumor cells were identified in the ascitic fluid. CAFs facilitated tumor cell aggregation and compaction to form MCAs, and enhanced the mesothelial clearance and adhesion abilities of tumor-cell MCAs. These findings suggest that ascitic CAFs promote peritoneal metastasis by forming heterotypic aggregates with tumor cells, and that they may serve as potential targets for the treatment of HGSOC.