Department of Medical Oncology, South West German Comprehensive Cancer Center, Tuebingen, Germany.
Stem Cells Transl Med. 2013 Jan;2(1):53-60. doi: 10.5966/sctm.2012-0055. Epub 2012 Dec 19.
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.
高级成人软组织肉瘤(STS)是一种罕见的肿瘤,预后不良,系统治疗选择有限。STS 可能起源于间充质干细胞(MSCs);后者主要从成人骨髓中分离出来,作为具有向间充质组织分化能力的贴壁细胞。最近,已经建立了一组抗体,允许对具有高选择性的原代 MSCs 进行前瞻性分离。与其他恶性肿瘤中的癌症干细胞类似,肉瘤干细胞可能与相应的前体细胞(即 MSCs)具有免疫表型相似性。因此,我们着手通过流式细胞术在肉瘤细胞系和原发肿瘤样本中建立 MSC 标志物的表达模式。此外,还检查了来自不同来源的成纤维细胞。结果证明肉瘤细胞共享大量 MSC 标志物。表达模式包括均匀表达的标志物,以及仅染色肉瘤细胞亚群的 MSC 标志物。W5C5、W8B2(组织非特异性碱性磷酸酶[TNAP])、CD344(卷曲蛋白 4)和 CD271 的表达标记出具有增加增殖潜力的亚群。此外,CD271+细胞在体外表现出多柔比星耐药性,并在无血清条件下形成球体的能力增加。有趣的是,另一组抗原,包括真正的祖细胞标志物 CD117 和 CD133,没有表达。展示了在肉瘤细胞、成纤维细胞和 MSCs 中新型 MSC 标志物的比较表达模式。我们的数据表明最常见的成人型肉瘤具有分级细胞结构,并提出 W5C5、TNAP、CD344 和 CD271 作为潜在的肉瘤祖细胞标志物。