Tumor cell‑fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer

Han,Qing; Huang,Bangxing; Huang,Zaiju; Cai,Jing; Gong,Lanqing; Zhang,Yifan; Jiang,Jiahong; Dong,Weihong; Wang,Zehua

doi:10.3892/ijmm.2019.4361

Tumor cell‑fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer

Authors:
- Qing Han
- Bangxing Huang
- Zaiju Huang
- Jing Cai
- Lanqing Gong
- Yifan Zhang
- Jiahong Jiang
- Weihong Dong
- Zehua Wang
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Affiliations: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: October 2, 2019 https://doi.org/10.3892/ijmm.2019.4361
Pages: 2245-2255
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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