肿瘤干细胞与滑膜肉瘤相关研究进展

20世纪50年代Makino等[1]通过肿瘤细胞自体移植实验发现肿瘤组织中极少数细胞具有干细胞特性能诱发新的肿瘤组织,首次提出肿瘤干细胞（cancerstem cells,CSCs）理论.该理论认为,肿瘤干细胞作为一类特殊的干细胞,具有自我更新能力和分化潜能,以及高致瘤性和耐药性的特点,可以通过分化为肿瘤细胞而产生肿瘤,即认为肿瘤干细胞是肿瘤启动、增殖生长、转移复发的根源.

Research advances related with cancer stem cells and synovial sarcoma

Cancer stem cells （CSCs） are identified and characterized as a unique stem cell in many types of cancer. Although there is no consensus regarding CSCs phenotype from different tumor types, CSCs from different cancers share a primitive undifferentiated nature. Current CSCs studies have provided many new insights into the complexities of cancer therapy： tumor initiation, self-renewal, multi-potential differentiation, high tumorigenicity, resistance to therapy and prediction of clinical course. There are 3 possible methodologies to isolate or identify cancer stem cells： the use of a magnetic activated cell sorting （MACS）, flowcytometry （FCM） identifying, or the measurement of aldehyde dehydrogenase （ALDH）. The novel promising therapies against cancer stem cells are considered, including targeting signal transduction pathways, surface molecular markers as well as differentiation-inducing therapy. Synovial sarcoma （SS） is a malignant soft tissue tumor characterized by its unique chromosomal translocation leading to the formation of the SS18-SSX fusion gene. However, the cellular origin of SS is highly debated. It has established 2 novel human SS cell lines, named Yamato-SS and Aska-SS. Their biological properties were investigated and the self- renewal ability of these cells to generate sarcospheres was found. SS traditionally has been considered to have a poor prognosis, however, not all SS shares the same dismal outcome. Additonally, cytogenetics has proven that certain molecular genetic features are related to the course of the disease and thus may be used as a prognostic indicator. Although primary therapy is predicated on surgical resection with an adequate margin and maximal preservation of function, adjuvant radiation and/or chemotherapy may be beneficial, particularly in high risk patients, whereas adjuvant chemotherapy, for localized respectable SS in adults. In this review, we discuss the current evidence regarding the identification and microenvironmental control of stem cell populations as well as exploring the evidence supporting the existence of CSCs population in SS. The characterization of the molecular phenotype of these CSCs, associated with an accurate definition of their typical derangement in cell differentiation, can represent a fundamental advance in terms of diagnosis and therapy of SS. Preliminary results seem to be promising but further studies are required to define the therapeutic index of this new anticancer treatment. Moreover, understanding the pathogenetic mechanisms of CSCs can expand the therapeutic applications of normal adult stem cells by reducing the risk of uncontrolled CSCs differentiation. So far no sufficient data shows the potential role of CSCs in the resistance against chemotherapy or radiation and presents challenging options for therapeutic interventions. In future, multi-institutional prospectively randomized, controlled studies will be needed to better define the role of CSCs.