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

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...

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Veröffentlicht in:International journal of molecular medicine 2019-12, Vol.44 (6), p.2245-2255
Hauptverfasser: Han, Qing, Huang, Bangxing, Huang, Zaiju, Cai, Jing, Gong, Lanqing, Zhang, Yifan, Jiang, Jiahong, Dong, Weihong, Wang, Zehua
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container_issue 6
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container_title International journal of molecular medicine
container_volume 44
creator Han, Qing
Huang, Bangxing
Huang, Zaiju
Cai, Jing
Gong, Lanqing
Zhang, Yifan
Jiang, Jiahong
Dong, Weihong
Wang, Zehua
description 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.
doi_str_mv 10.3892/ijmm.2019.4361
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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. 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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. 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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.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>31638162</pmid><doi>10.3892/ijmm.2019.4361</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Antigens
Ascites
Ascites - pathology
Ascitic Fluid - pathology
Cadherins - genetics
Cancer metastasis
Cancer research
Cancer therapies
Cancer-Associated Fibroblasts - metabolism
Cancer-Associated Fibroblasts - pathology
Cell Adhesion - genetics
Cell Aggregation - genetics
Cell Line, Tumor
Chemotherapy
Coculture Techniques
Cystadenocarcinoma, Serous - genetics
Cystadenocarcinoma, Serous - metabolism
Cystadenocarcinoma, Serous - pathology
Female
Fibroblasts
Genetic Heterogeneity
Humans
Immunoglobulins
Immunohistochemistry
Medical prognosis
Metastasis
Neoplasm Metastasis
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Patients
Peritoneal Neoplasms - genetics
Peritoneal Neoplasms - metabolism
Peritoneal Neoplasms - pathology
Peritoneal Neoplasms - secondary
Peritoneum - metabolism
Peritoneum - pathology
Phenotypes
Primary Cell Culture
Proteins
Scientific equipment industry
Spheroids, Cellular
Surgery
Tumors
title Tumor cell‑fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer
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