Dataset Information

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

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.

SUBMITTER: Han Q

PROVIDER: S-EPMC6844628 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Han Qing Q Huang Bangxing B Huang Zaiju Z Cai Jing J Gong Lanqing L Zhang Yifan Y Jiang Jiahong J Dong Weihong W Wang Zehua Z

International journal of molecular medicine 20191002 6

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 om ...[more]

PMID: 31638162

Similar Datasets

Project description:Ovarian cancer (OC) ranks among the deadliest cancers in women. Lack of symptoms, rapid spread of metastases and common chemoresistance contribute to unfortunate fate of majority of OC patients, especially those having high-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of OC. Many HGSC patients have excess fluid in the peritoneum at the stage of diagnosis called ascites. Ascites is basically a tumor microenvironment (TME) in the liquid form containing various cells, proteins and also extracellular vesicles (EVs). EVs are small membrane-bound particles that convey proteins, lipids and nucleic acids between cells and their cargo reflects the cell of origin. EVs play important role in cancerogenesis and hold great promise as disease biomarkers as well as potential therapeutic targets. Small size and polydispersity of EVs bring various challenges to their isolation and characterization, including method-dependent enrichment of different EV subtypes as well as contaminants. We isolated EVs from ascites of 11 patients by two different methods (ultracentrifugation coupled to sucrose cushion and size-exclusion chromatography, qEV column) and analyzed them by mass spectrometry. We identified core ascitic EV proteins present in all patients that contain typical EV markers and are devoid of method-dependent contaminants. To cover interpatient heterogeneity, we expanded this “core proteome” with proteins found in majority of patients. Next, we compared them with proteins of EVs from related control fluids and uncovered proteins present only on EVs from HGSC patients. We believe this list of proteins contain both important players of HGSC progression as well as potential biomarkers. Using single cell RNA sequencing data, we mapped the origin of EVs to different types of cells present in malignant ascites. Our results suggest that EVs in ascites do not come predominantly from tumor cells, but rather from variety of non-malignant cell types including cancer-associated fibroblasts and tumor-associated macrophages, which presence in ascites was confirmed by flow cytometry. This emphasizes the recently appreciated role of TME in the progression of HGSC. To conclude, this is the first study attempting to link EV composition to the cell types producing it. As such it opens numerous avenues both for better understanding of EV role in tumor promotion/prevention and for the improved HGSC diagnostics.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets