Cargando…

Role of malignant ascites on human mesothelial cells and their gene expression profiles

BACKGROUND: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believ...

Descripción completa

Detalles Bibliográficos
Autores principales: Matte, Isabelle, Lane, Denis, Bachvarov, Dimcho, Rancourt, Claudine, Piché, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008408/
https://www.ncbi.nlm.nih.gov/pubmed/24761768
http://dx.doi.org/10.1186/1471-2407-14-288
_version_ 1782314441933586432
author Matte, Isabelle
Lane, Denis
Bachvarov, Dimcho
Rancourt, Claudine
Piché, Alain
author_facet Matte, Isabelle
Lane, Denis
Bachvarov, Dimcho
Rancourt, Claudine
Piché, Alain
author_sort Matte, Isabelle
collection PubMed
description BACKGROUND: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. METHODS: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. RESULTS: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-κB survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. CONCLUSIONS: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions.
format Online
Article
Text
id pubmed-4008408
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-40084082014-05-03 Role of malignant ascites on human mesothelial cells and their gene expression profiles Matte, Isabelle Lane, Denis Bachvarov, Dimcho Rancourt, Claudine Piché, Alain BMC Cancer Research Article BACKGROUND: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. METHODS: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. RESULTS: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-κB survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. CONCLUSIONS: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions. BioMed Central 2014-04-24 /pmc/articles/PMC4008408/ /pubmed/24761768 http://dx.doi.org/10.1186/1471-2407-14-288 Text en Copyright © 2014 Matte et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research Article
Matte, Isabelle
Lane, Denis
Bachvarov, Dimcho
Rancourt, Claudine
Piché, Alain
Role of malignant ascites on human mesothelial cells and their gene expression profiles
title Role of malignant ascites on human mesothelial cells and their gene expression profiles
title_full Role of malignant ascites on human mesothelial cells and their gene expression profiles
title_fullStr Role of malignant ascites on human mesothelial cells and their gene expression profiles
title_full_unstemmed Role of malignant ascites on human mesothelial cells and their gene expression profiles
title_short Role of malignant ascites on human mesothelial cells and their gene expression profiles
title_sort role of malignant ascites on human mesothelial cells and their gene expression profiles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008408/
https://www.ncbi.nlm.nih.gov/pubmed/24761768
http://dx.doi.org/10.1186/1471-2407-14-288
work_keys_str_mv AT matteisabelle roleofmalignantascitesonhumanmesothelialcellsandtheirgeneexpressionprofiles
AT lanedenis roleofmalignantascitesonhumanmesothelialcellsandtheirgeneexpressionprofiles
AT bachvarovdimcho roleofmalignantascitesonhumanmesothelialcellsandtheirgeneexpressionprofiles
AT rancourtclaudine roleofmalignantascitesonhumanmesothelialcellsandtheirgeneexpressionprofiles
AT pichealain roleofmalignantascitesonhumanmesothelialcellsandtheirgeneexpressionprofiles