Division of Pediatric Oncology, Department of Pediatrics, Columbia University Medical Center , New York, NY , USA.
Front Oncol. 2013 Jun 27;3:168. doi: 10.3389/fonc.2013.00168. Print 2013.
Sarcomas represent a clinically and biologically diverse group of malignant connective tissue tumors. Despite aggressive conventional therapy, a large proportion of sarcoma patients experience disease recurrence which will ultimately result in mortality. The presence of a unique population of cells, referred to as cancer stem cells (CSCs), have been proposed to be responsible for refractory responses to current chemotherapies as well underlying the basis for metastasis and relapse of disease - clinical corollaries to what has been termed the CSC hypothesis. The presence of CSCs have been suggested in a variety of hematologic and solid malignancies, and only more recently in sarcomas. Based on our current understanding of normal stem cell biology and evidence obtained from the study of malignant hematopoietic and solid tumors, researchers have identified candidate cell surface markers (CD133, CD117, Stro-1), biochemical markers (aldehyde dehydrogenase activity), and cytological characteristics (side population and spherical colony formation) that may identify putative sarcoma CSCs. In this review, we explore the current state of evidence that may suggest the existence of sarcoma CSCs. We present research in osteosarcoma, the Ewing's sarcoma family of tumors, rhabdomyosarcoma, as well as other sarcoma subtypes to describe commonly used molecular and biochemical markers, as well as techniques, used in the identification, isolation, and characterization of candidate sarcoma CSCs. We will also discuss the current controversies and challenges that face research in sarcoma CSC.
肉瘤是一组临床上和生物学上具有显著异质性的恶性结缔组织肿瘤。尽管采用了积极的常规治疗，仍有很大一部分肉瘤患者会经历疾病复发，最终导致死亡。有一种独特的细胞群体，被称为癌症干细胞（CSCs），它们被认为是导致对现有化疗药物产生耐药性的原因，也是疾病转移和复发的基础——这与所谓的 CSC 假说的临床推论相一致。CSCs 存在于多种血液系统和实体恶性肿瘤中，最近才在肉瘤中被发现。基于我们对正常干细胞生物学的现有理解以及从恶性造血系统和实体肿瘤研究中获得的证据，研究人员已经确定了候选细胞表面标志物（CD133、CD117、Stro-1）、生化标志物（乙醛脱氢酶活性）和细胞学特征（侧群和球形集落形成），这些标志物可能鉴定出潜在的肉瘤 CSCs。在这篇综述中，我们探讨了目前可能表明肉瘤 CSCs 存在的证据。我们介绍了骨肉瘤、尤文肉瘤家族肿瘤、横纹肌肉瘤以及其他肉瘤亚型的研究，以描述用于鉴定、分离和表征候选肉瘤 CSCs 的常用分子和生化标志物以及技术。我们还将讨论肉瘤 CSC 研究面临的当前争议和挑战。
