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 |
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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. 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.</description><identifier>ISSN: 1107-3756</identifier><identifier>EISSN: 1791-244X</identifier><identifier>DOI: 10.3892/ijmm.2019.4361</identifier><identifier>PMID: 31638162</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>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</subject><ispartof>International journal of molecular medicine, 2019-12, Vol.44 (6), p.2245-2255</ispartof><rights>COPYRIGHT 2019 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2019</rights><rights>Copyright: © Han et al. 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-154a8e6121f1ee6afa295413b22151e431c48681164778ba89b747beacbfcabb3</citedby><cites>FETCH-LOGICAL-c485t-154a8e6121f1ee6afa295413b22151e431c48681164778ba89b747beacbfcabb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31638162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Qing</creatorcontrib><creatorcontrib>Huang, Bangxing</creatorcontrib><creatorcontrib>Huang, Zaiju</creatorcontrib><creatorcontrib>Cai, Jing</creatorcontrib><creatorcontrib>Gong, Lanqing</creatorcontrib><creatorcontrib>Zhang, Yifan</creatorcontrib><creatorcontrib>Jiang, Jiahong</creatorcontrib><creatorcontrib>Dong, Weihong</creatorcontrib><creatorcontrib>Wang, Zehua</creatorcontrib><title>Tumor cell‑fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer</title><title>International journal of molecular medicine</title><addtitle>Int J Mol Med</addtitle><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.</description><subject>Antigens</subject><subject>Ascites</subject><subject>Ascites - pathology</subject><subject>Ascitic Fluid - pathology</subject><subject>Cadherins - genetics</subject><subject>Cancer metastasis</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cancer-Associated Fibroblasts - metabolism</subject><subject>Cancer-Associated Fibroblasts - pathology</subject><subject>Cell Adhesion - genetics</subject><subject>Cell Aggregation - genetics</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Coculture Techniques</subject><subject>Cystadenocarcinoma, Serous - genetics</subject><subject>Cystadenocarcinoma, Serous - metabolism</subject><subject>Cystadenocarcinoma, Serous - pathology</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Genetic Heterogeneity</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunohistochemistry</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Neoplasm Metastasis</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Patients</subject><subject>Peritoneal Neoplasms - genetics</subject><subject>Peritoneal Neoplasms - metabolism</subject><subject>Peritoneal Neoplasms - pathology</subject><subject>Peritoneal Neoplasms - secondary</subject><subject>Peritoneum - metabolism</subject><subject>Peritoneum - pathology</subject><subject>Phenotypes</subject><subject>Primary Cell Culture</subject><subject>Proteins</subject><subject>Scientific equipment industry</subject><subject>Spheroids, Cellular</subject><subject>Surgery</subject><subject>Tumors</subject><issn>1107-3756</issn><issn>1791-244X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkc9u1DAQxiMEoqVw5Ygicd4lYzuOc0GqKv5JlbgUiZs19k6yXiX2Yntb9cYr8AZ9lj4KT4IjSgGp8mGsmd98-kZfVb2EZs1Vz9643TyvWQP9WnAJj6pj6HpYMSG-Pi5_aLoV71p5VD1Ladc0rBW9elodcZBcgWTH1ebiMIdYW5qmn99_DM7EYCZMud5Sphjy9d7ZGscx0oiZUu387c2Mkxs9-lxjsm7phqHeY3bkc6qvXN7W4RKjQ19b9Jbi8-rJgFOiF3f1pPry_t3F2cfV-ecPn85Oz1dWqDavoBWoSAKDAYgkDsj6VgA3jEELJDgUTioAKbpOGVS96URnCK0ZLBrDT6q3v3X3BzPTxhY_ESe9j27GeK0DOv3_xLutHsOllkoIyVQReH0nEMO3A6Wsd-EQffGsGQfeN50A9pcacSLt_BCKmJ1dsvpUNrIXou1kodYPUOVtaHY2eBpc6T-0YGNIKdJwbxwavYStl7D1ErZewi4Lr_499x7_ky7_BfhKqP4</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Han, Qing</creator><creator>Huang, Bangxing</creator><creator>Huang, Zaiju</creator><creator>Cai, Jing</creator><creator>Gong, Lanqing</creator><creator>Zhang, Yifan</creator><creator>Jiang, Jiahong</creator><creator>Dong, Weihong</creator><creator>Wang, Zehua</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. 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pathology</topic><topic>Ascitic Fluid - pathology</topic><topic>Cadherins - genetics</topic><topic>Cancer metastasis</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cancer-Associated Fibroblasts - metabolism</topic><topic>Cancer-Associated Fibroblasts - pathology</topic><topic>Cell Adhesion - genetics</topic><topic>Cell Aggregation - genetics</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Coculture Techniques</topic><topic>Cystadenocarcinoma, Serous - genetics</topic><topic>Cystadenocarcinoma, Serous - metabolism</topic><topic>Cystadenocarcinoma, Serous - pathology</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Genetic Heterogeneity</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunohistochemistry</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Neoplasm Metastasis</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Patients</topic><topic>Peritoneal Neoplasms - genetics</topic><topic>Peritoneal Neoplasms - metabolism</topic><topic>Peritoneal Neoplasms - pathology</topic><topic>Peritoneal Neoplasms - secondary</topic><topic>Peritoneum - metabolism</topic><topic>Peritoneum - pathology</topic><topic>Phenotypes</topic><topic>Primary Cell Culture</topic><topic>Proteins</topic><topic>Scientific equipment industry</topic><topic>Spheroids, Cellular</topic><topic>Surgery</topic><topic>Tumors</topic><toplevel>online_resources</toplevel><creatorcontrib>Han, Qing</creatorcontrib><creatorcontrib>Huang, Bangxing</creatorcontrib><creatorcontrib>Huang, Zaiju</creatorcontrib><creatorcontrib>Cai, Jing</creatorcontrib><creatorcontrib>Gong, Lanqing</creatorcontrib><creatorcontrib>Zhang, Yifan</creatorcontrib><creatorcontrib>Jiang, Jiahong</creatorcontrib><creatorcontrib>Dong, Weihong</creatorcontrib><creatorcontrib>Wang, Zehua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Qing</au><au>Huang, Bangxing</au><au>Huang, Zaiju</au><au>Cai, Jing</au><au>Gong, Lanqing</au><au>Zhang, Yifan</au><au>Jiang, Jiahong</au><au>Dong, Weihong</au><au>Wang, Zehua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor cell‑fibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer</atitle><jtitle>International journal of molecular medicine</jtitle><addtitle>Int J Mol Med</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>44</volume><issue>6</issue><spage>2245</spage><epage>2255</epage><pages>2245-2255</pages><issn>1107-3756</issn><eissn>1791-244X</eissn><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.</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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