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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-53100

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.

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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.


13 citations in Web of Science®
14 citations in Scopus®
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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
Deposited On:04 Jan 2012 10:22
Last Modified:05 Apr 2016 15:15
Publisher:Oxford University Press
Publisher DOI:10.1093/carcin/bgr127
PubMed ID:21729925

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