Fulltext

Pleural mesothelioma side populations have a precursor phenotype

Frei, Claudia ; Opitz, Isabelle ; Soltermann, Alex ; Fischer, Bruno ; Moura, Ubiratan ; Rehrauer, Hubert ; Weder, Walter ; Stahel, Rolf ; Felley-Bosco, Emanuela

In: Carcinogenesis, 2011, vol. 32, no. 9, p. 1324-1332

Ajouter à la liste personnelle
    Titre
    • Pleural mesothelioma side populations have a precursor phenotype
    Auteur
    • Frei, Claudia. Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Haeldeliweg 4, 8044 Zurich, Switzerland
    • Opitz, Isabelle. Division of Thoracic Surgery, and
    • Soltermann, Alex. Institute of Surgical Pathology, University Hospital Zürich, Haeldeliweg 8091 Zürich, Switzerland
    • Fischer, Bruno. Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Haeldeliweg 4, 8044 Zurich, Switzerland
    • Moura, Ubiratan. Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Haeldeliweg 4, 8044 Zurich, Switzerland
    • Rehrauer, Hubert. Functional Genomic Center Zurich, 8057 Zurich, Switzerland
    • Weder, Walter. Division of Thoracic Surgery, and
    • Stahel, Rolf. Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Haeldeliweg 4, 8044 Zurich, Switzerland
    • Felley-Bosco, Emanuela. E-mail: emanuela.felley-bosco@usz.ch
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Carcinogenesis, 2011, vol. 32, no. 9, p. 1324-1332. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:290673
    Summary
    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 CD105high 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