骨肉瘤肿瘤干细胞的研究现状、争议和思考  

Research on cancer stem cells in osteosarcoma： current status, controversy and comment

作　　者：周振华[1] 肖建如[1] Zhou Zhenhua;Xiao Jianru(Department of Orthopaedic Oncology,Changzheng Hospital,The Second Military Medical University,Shanghai 200003,China)

机构地区：[1]第二军医大学(海军军医大学)附属长征医院骨肿瘤外科,200003

出　　处：《中华骨科杂志》2018年第18期1135-1142,共8页Chinese Journal of Orthopaedics

基　　金：国家自然科学基金（81772857）

摘　　要：骨肉瘤是最常见的原发恶性骨肿瘤之一，好发于儿童和青少年，一旦出现转移往往预后不佳。临床上骨肉瘤经常出现化疗耐药情况，亟需新的治疗方式和治疗靶点。肿瘤干细胞学说的出现吸引了众多从事骨肉瘤生物学研究者的目光，已有的研究表明骨肉瘤由多种不同功能的肿瘤细胞亚群构成，其中只有一小部分骨肉瘤细胞具有肿瘤干细胞的特征，例如自我更新和多向分化能力，这些能力使骨肉瘤干细胞能够分化成不同类型的肿瘤细胞；除此之外骨肉瘤干细胞在骨肉瘤的增殖、侵袭、复发和转移中发挥着决定性的作用，这些研究表明骨肉瘤的发生可能与肿瘤干细胞的存在密切相关。可能的机制是肿瘤干细胞自我更新途径有别于正常组织干细胞。骨肉瘤干细胞的发现为理解骨肉瘤的生物学特性提供了新的视野，但是未来仍然需要更进一步的研究来了解正常组织干细胞和肿瘤干细胞在骨肉瘤发生、发展中的作用，各种信号通路调节正常组织干细胞和肿瘤干细胞自我更新的途径，以及相关的信号通路失调导致肿瘤发生的机制。我们期望通过骨肉瘤干细胞的研究最终可以寻找到骨肉瘤新的治疗靶点以及预警分子，给提高骨肉瘤患者的预后甚至根治骨肉瘤带来希望。在本文中我们总结了近年骨肉瘤干细胞的研究进展，包括骨肉瘤干细胞分离技术和现有的分子标志等，并且针对骨肉瘤干细胞研究领域的一些争议进行了探讨。Osteosarcoma is the most common primary malignant tumor of bone in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis. Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. The composition of cancer stem cells is one of the attractive theoretical studies in osteosarcoma biology. It has been proposed that osteosarcomas are composed of a group of functionally heterogeneous cells. Only a small number of osteosarcoma cells have stem cell characteristics, with serf-renewal and differentiation capacities, which facilitates in the generation of different types of osteosarcoma cells. These osteosarcoma stem cells play a decisive role in maintaining the proliferation, invasion, recurrence, and metastasis of tumors. Previ- ous research suggests that osteosarcoma formation may result from the development of cancer stem cells by the deregulation of nor- mal self-renewal pathways of tissue stem cells. The discovery of cancer stem cells in osteosarcoma offers a new approach to under- standing the biology of these conditions. Further study is needed to understand both normal and osteosarcoma stem cell develop- ment and various signaling pathways which appear to regulate serf-renewal of stem cells and CSCs, with dysregulation of these sig- naling pathways leading to tumorigenesis. Ultimately, new prognostic and predictive markers, as well as targeted therapeutic strate- gies, may be developed to force osteosarcoma into better outcome or permanent remission. In this review we will discuss the re- search advance of cancer stem cells in osteosarcoma such as commonly used isolation techniques for osteosarcoma stem cells as well as the identified biochemical and molecular markers and we share our viewpoints on controversy in research of osteosarcoma stem cells.

关 键 词：骨肉瘤细胞 肿瘤干细胞 细胞自我更新 组织干细胞 原发恶性骨肿瘤 生物学特性 分化能力 细胞分离技术 

分 类 号：R738.1[医药卫生—肿瘤]