Tumor cellfibroblast heterotypic aggregates in malignant ascites of patients with ovarian cancer.
Int J Mol Med
; 44(6): 2245-2255, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31638162
ABSTRACT
Ascitic multicellular aggregates (MCAs) promote peritoneal metastasis of ovarian cancer. The aim of the present study was to elucidate the role of cancerassociated fibroblasts (CAFs) in MCA formation and metastasis in patients with highgrade 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 tumorcell MCA formation was assessed by coculture 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 tumorcell 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Neoplasias Peritoneais
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Cistadenocarcinoma Seroso
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Fibroblastos Associados a Câncer
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2019
Tipo de documento:
Article