title: Shared cell surface marker expression in mesenchymal stem cells and adult sarcomas.
abstract: Advanced adult soft-tissue sarcomas (STSs) are rare tumors with a dismal prognosis and limited systemic treatment options. STSs may originate from mesenchymal stem cells (MSCs); the latter have mainly been isolated from adult bone marrow as plastic-adherent cells with differentiation capacity into mesenchymal tissues. Recently, a panel of antibodies has been established that allows for the prospective isolation of primary MSCs with high selectivity. Similar to cancer stem cells in other malignancies, sarcoma stem cells may bear immunophenotypic similarity with the corresponding precursor, that is, MSCs. We therefore set out to establish the expression pattern of MSC markers in sarcoma cell lines and primary tumor samples by flow cytometry. In addition, fibroblasts from different sources were examined. The results document a significant amount of MSC markers shared by sarcoma cells. The expression pattern includes uniformly expressed markers, as well as MSC markers that only stained subpopulations of sarcoma cells. Expression of W5C5, W8B2 (tissue nonspecific alkaline phosphatase [TNAP]), CD344 (frizzled-4), and CD271 marked subpopulations displaying increased proliferation potential. Moreover, CD271+ cells displayed in vitro doxorubicin resistance and an increased capacity to form spheres under serum-free conditions. Interestingly, another set of antigens, including the bona fide progenitor cell markers CD117 and CD133, were not expressed. Comparative expression patterns of novel MSC markers in sarcoma cells, as well as fibroblasts and MSCs, are presented. Our data suggest a hierarchical cytoarchitecture of the most common adult type sarcomas and introduce W5C5, TNAP, CD344, and CD271 as potential sarcoma progenitor cell markers.
authors.affiliation: Department of Medical Oncology, South West German Comprehensive Cancer Center, Tuebingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirths
authors.forename: Elke
authors.initials: E
authors.lastname: Malenke
authors.forename: Torsten
authors.initials: T
authors.lastname: Kluba
authors.forename: Simone
authors.initials: S
authors.lastname: Rieger
authors.forename: Martin R
authors.initials: MR
authors.lastname: Müller
authors.forename: Sabine
authors.initials: S
authors.lastname: Schleicher
authors.forename: Claus
authors.initials: C
authors.lastname: Hann von Weyhern
authors.forename: Florian
authors.initials: F
authors.lastname: Nagl
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Wichard
authors.initials: W
authors.lastname: Vogel
authors.forename: Frank
authors.initials: F
authors.lastname: Mayer
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kopp
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D004317:Doxorubicin