UZH-Logo

Maintenance Infos

Pleural mesothelioma side populations have a precursor phenotype


Frei, C; Opitz, I; Soltermann, A; Fischer, B; Moura, U; Rehrauer, H; Weder, W; Stahel, R; Felley-Bosco, E (2011). Pleural mesothelioma side populations have a precursor phenotype. Carcinogenesis, 32(9):1324-1332.

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.

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.

Citations

13 citations in Web of Science®
15 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 04 Jan 2012
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:04 Jan 2012 10:22
Last Modified:05 Apr 2016 15:15
Publisher:Oxford University Press
ISSN:0143-3334
Publisher DOI:https://doi.org/10.1093/carcin/bgr127
PubMed ID:21729925

Download

[img]
Content: Published Version
Filetype: PDF - Registered users only
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations