Pleural mesothelioma side populations have a precursor phenotype.
Details
Serval ID
serval:BIB_CD3C2AEE40F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pleural mesothelioma side populations have a precursor phenotype.
Journal
Carcinogenesis
ISSN
1460-2180 (Electronic)
ISSN-L
0143-3334
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
32
Number
9
Pages
1324-1332
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
DyeCycleViolet was used to set up the side population (SP) functional assay aimed at identifying subpopulations of malignant pleural mesothelioma (MPM) tumor cells with chemoresistance phenotype associated with ABCG2 transporter activity. Self-renewal, chemoresistance and tumorigenicity were tested for SP and non-side population (NSP) cells. Tumors were characterized by mesothelin, calretinin, N-cadherin, D2-40 and Wilms tumor 1 (WT1) immunohistochemistry. Surface expression of mesenchymal stem cell markers CD90, CD73 and CD105 was investigated in SP and NSP cells. We identified SP cells with self-renewal properties and increased chemoresistance in MPM cell lines and tumor-derived primary cell cultures. Compared with the non-SP fraction (NSP), the SP fraction led to the development of tumors including cells with mesothelium precursor phenotype characterized by mesenchymal morphology, being WT1 negative but cytoplasmic D2-40 positive and having a tendency of increased tumorigenicity. The same phenotypic shift was observed in patients with relapsing tumors after chemotherapy. Furthermore, the SP cells were enriched in CD105(-)(/low) expressing cells, which were small sized and had increased tumorigenicity compared with CD105(high) cells. Taken together, our results support the hypothesis that MPM CD105(-)(/low), chemoresistant small sized SP cells may constitute the cellular pool out of which recurrence develops. Further characterization of mechanisms of chemoresistance and self-renewal should lead to targets specific for this subpopulation in MPM patients.
Keywords
Animals, Antigens, CD/analysis, Drug Resistance, Neoplasm, HL-60 Cells, Humans, Mesothelioma/drug therapy, Mesothelioma/pathology, Mice, Mice, SCID, Phenotype, Pleural Neoplasms/drug therapy, Pleural Neoplasms/pathology, Receptors, Cell Surface/analysis, WT1 Proteins/analysis
Pubmed
Web of science
Open Access
Yes
Create date
03/08/2014 13:41
Last modification date
20/08/2019 15:47