肿瘤干细胞与肿瘤的诊断、转归和预后的关系

肿瘤干细胞(cancer stem cells,CSCs)是近年来干细胞研究和肿瘤研究的热点之一,它具有强大的自我更新和致瘤能力以及不断分化的潜能。目前研究发现肿瘤治疗后易复发、预后差、具有强耐药性与肿瘤中存在肿瘤干细胞有密切的关系。且肿瘤干细胞学说认为,肿瘤很可能是肿瘤干细胞产生的,并且已有学者和专家在造血系统肿瘤和多种实体瘤中分离并鉴定出肿瘤干细胞。对肿瘤干细胞、肿瘤干细胞与肿瘤的发生、发展、诊断、治疗及预后之间的关系作一综述。     

干细胞、肿瘤干细胞与肿瘤的关系

干细胞理论认为肿瘤是一种干细胞疾病，该理论为肿瘤的研究及治疗提供了新的方向和靶点。干细胞(stem cell)是一类具有自我更新和增殖分化能力的细胞，肿瘤细胞是一类具有无限增殖和失去分化为成熟细胞能力的细胞，肿瘤干细胞(cancer stem cell)是存在于肿瘤组织中的一小部分具有干细胞性质的细胞群体，能够驱使肿瘤的形成。本文拟综述干细胞、肿瘤干细胞与肿瘤发生发展之间的关系，为肿瘤的研究及临床治疗提供参考。     

肿瘤干细胞和肿瘤关系的研究进展

肿瘤干细胞在维持肿瘤细胞的分化、增殖及凋亡中发挥着重要作用.大量研究表明,肿瘤的发生、转移和复发与肿瘤干细胞的异常表达密切相关,这也许会成为肿瘤治疗的新靶点.因此研究肿瘤干细胞的起源及其与肿瘤的发生关系,成为当前研究和治疗肿瘤领域的新热点.本文就肿瘤干细胞与肿瘤发生的关系作简要的综述.     

干细胞niche与肿瘤干细胞产生和发展的关系

肿瘤干细胞学说认为大部分肿瘤来源于肿瘤干细胞。肿瘤干细胞与正常干细胞一样具有自我更新能力,能够产生肿瘤组织团块中的各种增殖和分化的细胞。肿瘤干细胞可能来源于正常干细胞或分化细胞。干细胞niche是干细胞生存的微环境,通过提供抑制细胞增殖和生长的信号来维持干细胞于静止状态。干细胞niche功能异常会导致niche的数量增加,以及干细胞功能异常和数量增加。肿瘤干细胞可能在异常的niche中存活,打破这种异常的niche就会削弱肿瘤干细胞的自我更新,从而抑制肿瘤的生长。靶向肿瘤干细胞异常微环境的治疗策略可能是癌症治疗的一个方向。     

干细胞、肿瘤干细胞与造血系统肿瘤

随着干细胞研究的不断深入，人们对胚胎干细胞(ES)、造血干细胞等干细胞了解日益加深。发现干细胞与肿瘤细胞有许多共性，如无限增生能力、迁移能力及在某些条件下能相互转化。提出肿瘤起源于干细胞、肿瘤中存在肿瘤干细胞等学说。这些学说的理论依据多来源于对造血系统肿瘤的研究。     

干细胞、肿瘤干细胞与造血系统肿瘤

随着干细胞研究的不断深入,人们对胚胎干细胞(ES)、造血干细胞等干细胞了解日益加深.发现干细胞与肿瘤细胞有许多共性,如无限增生能力、迁移能力及在某些条件下能相互转化.提出肿瘤起源于干细胞、肿瘤中存在肿瘤干细胞等学说.这些学说的理论依据多来源于对造血系统肿瘤的研究.     

甲状腺干细胞及其与甲状腺肿瘤干细胞的关系

甲状腺干细胞是存在于甲状腺组织内具有自我更新及增殖分化潜能的细胞.甲状腺肿瘤干细胞是甲状腺肿瘤组织中与甲状腺干细胞相似的细胞,是甲状腺肿瘤发生发展的细胞来源.研究表明,甲状腺干细胞是甲状腺肿瘤干细胞的重要来源,其恶变时所处的分化阶段对甲状腺肿瘤的恶性程度有重要影响.     

干细胞、肿瘤干细胞和SP细胞的关系及其研究进展

正常干细胞与肿瘤干细胞有许多相似之处，肿瘤干细胞可能起源于干细胞积累的突变。干细胞和肿瘤细胞均存在着SP细胞，SP细胞具有干细胞特性并高表达肿瘤多耐药蛋白ABCG2／BCRP1，SP细胞可能是肿瘤产生耐药和复发的原因。SP细胞为干细胞和肿瘤干细胞研究提供了有用的工具。     

肿瘤干细胞标志物与胃癌关系的研究进展

肿瘤干细胞（cancer stem cell,CSCs）是理论认为肿瘤中存在一小部分细胞具有自我更新和多向分化的潜能,具有特异性表面标志的细胞.目前已经从乳腺癌、结直肠癌、皮肤癌等多种恶性肿瘤中鉴定分离出了各自的肿瘤干细胞标志物.本文就与胃癌相关的干细胞标志物进行综述.     

干细胞肿瘤干细胞与肝细胞癌发生关系研究进展

越来越多的实验结果证实肿瘤起源于干细胞,诸如白血病、乳腺癌、脑肿瘤等已成功分离出肿瘤干细胞,有关肝干细胞与肝癌的研究较为成熟,理论上应存在肝癌干细胞,但因缺乏特异性标志物,相关的肝癌干细胞分离尚未成功.     

肿瘤干细胞的研究进展

肿瘤干细胞是存在于肿瘤中的一小部分具有干细胞性质的细胞群,具有高度的致瘤性和耐药性。同正常干细胞一样,肿瘤干细胞具有无限的自我更新和多向分化的潜能,使肿瘤在体内不断扩大或形成新的肿瘤,导致肿瘤复发和转移。肿瘤干细胞的研究有助于认识和理解肿瘤发生发展的机制,指导肿瘤的临床治疗。     

肿瘤干细胞的研究进展

肿瘤干细胞是存在于肿瘤中的一小部分具有干细胞性质的细胞群,具有高度的致瘤性和耐药性。同正常干细胞一样,肿瘤干细胞具有无限的自我更新和多向分化的潜能,使肿瘤在体内不断扩大或形成新的肿瘤,导致肿瘤复发和转移。肿瘤干细胞的研究有助于认识和理解肿瘤发生发展的机制,指导肿瘤的临床治疗。     

Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.     

实体瘤干细胞研究进展

新近的研究结果表明,肿瘤细胞在成瘤性方面存在不均一性。肿瘤中存在少量具有自我更新和高增殖能力的干细胞,它们在维持肿瘤生长中起决定性作用。该理论首先在血液系统肿瘤中取得突破,并在部分实体瘤如乳腺癌、脑肿瘤、前列腺肿瘤、肺癌、胰腺癌及部分细胞系中成功分离出了肿瘤干细胞。目前实体瘤干细胞的标志研究主要集中于CD133、CD44、CD117和CD34等CD分子。干细胞的识别将为肿瘤病理的认识及肿瘤治疗提供新的思路和方法。     

端粒和端粒酶与肿瘤干细胞的研究现状

目的:总结国内外对端粒、端粒酶与肿瘤起源、肿瘤干细胞的病理研究现状。方法:应用检索MED-LINE及CHKD期刊全文数据库检索系统,以"端粒、端粒酶和肿瘤干细胞"为关键词,检索1997-2008年有关文献。纳入标准:端粒、端粒酶与肿瘤干细胞的论著性文章。根据标准,纳入分析24篇参考文献。结果:端粒酶激活和端粒稳定对肿瘤干细胞演进是必需的,端粒酶激活是肿瘤干细胞自我更新和不定向分化的必要条件,端粒的动力学代表肿瘤干细胞恶性来源和有丝分裂历史,分析肿瘤干细胞端粒长度,端粒酶活性和细胞遗传学特性有助于揭示肿瘤干细胞起源和肿瘤形成历史,从而深化对肿瘤病理的认识,为恶性肿瘤治疗提供依据。结论:端粒和端粒酶在肿瘤干细胞中表达,是消灭肿瘤理想的靶标,有待进一步研究总结。     

Mesenchymal stem cells in lung cancer tumor microenvironment: their biological properties,influence on tumor growth and therapeutic implications

The tumor microenvironment (TME) of lung cancer has been documented to play an important role in participating in tumor disease progression. As the precursor of most stroma in TME, mesenchymal stem cells (MSCs) draw great attention since evidence has suggested that MSCs derived from lung cancer patients present a different phenotype compared to their normal counterparts. Furthermore, MSCs could be recruited towards tumor sites and influence tumor survival, although the effect remains contradictory. Our review will summarize the current advance of the role MSCs in lung cancer and explore the possible treatment strategies by blocking their crosstalk.     

Lung cancer stem cells: Progress and prospects

Epithelial stem cells are critical for tissue generation during development and for repair following injury. In both gestational and postnatal stages, the highly branched and compartmentalized organization of the lung is maintained by multiple, resident stem/progenitor cell populations that are responsible for the homeostatic maintenance and injury repair of pulmonary epithelium. Though lung epithelial injury in the absence of oncogenic mutation is more commonly expressed as chronic lung disease, lung cancer is the most common form of death worldwide and poses a highly significant risk to human health. Cancer is defined by the cell of origin, responsible for initiating the disease. The Cancer Stem Cell Hypothesis proposes that cancer stem cells, identified by stem-like properties of self-renewal and generation of differentiated progeny, are responsible for propagating growth and spread of the disease. In lung cancer, it is hypothesized that cancer stem cells derive from several possible cell sources. The stem cell-like resistance to injury and proliferative potentials of bronchioalveolar stem cells (BASCs) and alveolar epithelial type II cells (AEC2), as well as cells that express the cancer stem cell marker glycoprotein prominin-1 (CD133) or markers for side populations make them potential reservoirs of lung cancer stem cells. The abnormal activation of pathways that normally regulate embryonic lung development, as well as adult tissue maintenance and injury repair, including the Wnt, Hedgehog (Hh) and Notch pathways, has also been identified in lung tumor cells. It is postulated that therapies for lung cancer that specifically target stem cell signaling pathways utilized by lung cancer stem cells could be beneficial in combating this disease.     

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3-4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents.