甲状腺肿瘤干细胞研究进展

肿瘤干细胞已经成为肿瘤发病机制的研究热点,并且已经在很多肿瘤中发现并分离出了肿瘤干细胞.甲状腺肿瘤干细胞模型也已经被提出,越来越多的实验研究支持甲状腺肿瘤干细胞的存在,并认为他们可能来源于甲状腺干细胞.本文综述了目前甲状腺干细胞和甲状腺肿瘤干细胞的研究进展.     

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.     

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.     

肿瘤干细胞研究进展

肿瘤研究的基本问题之一是哪些肿瘤细胞能够无限生长.传统理论认为肿瘤生长是所有肿瘤细胞一起增殖的结果.最近通过对造血系肿瘤的研究发现肿瘤细胞的生长繁殖和干细胞之间有许多惊人的相似之处,提出了肿瘤干细胞学说,认为肿瘤生长是肿瘤组织中极少量具有特殊细胞表面标志的肿瘤干细胞增殖的结果.研究证明人类急性髓性白血病(AML)中的肿瘤干细胞存在于CD34 /CD38亚群中,而人乳腺癌中的肿瘤干细胞属于ESA CD44 CD24-/low亚群.肿瘤干细胞概念的提出,提供了靶向性或选择性杀伤肿瘤干细胞从而根治肿瘤和防止肿瘤复发和转移的可能性.研究肿瘤干细胞特异性的生物学特点,对肿瘤的发生、发展和转归的理论以及肿瘤的诊断、预防和治疗均有重要意义.     

转移肿瘤干细胞在肿瘤转移中作用机制的研究进展

随着肿瘤干细胞学说的提出及其在肿瘤发生中所起重要作用的不断研究,更多学者将目光聚焦在肿瘤干细胞与肿瘤转移的关系上,认为肿瘤干细胞可能是引起肿瘤转移的元凶,并进一步提出了转移肿瘤干细胞的概念.肿瘤转移是一个复杂的多因素参与的病理过程,上皮间质转化机制、基质细胞衍生因子-1(stromal cell-derived factor 1,SDF-1)/ 趋化因子受体4 [chemokine(Cys-X-Cys motif) receptor 4,CXCR4]和肿瘤干细胞及其微环境等都在肿瘤转移的过程中起到了不可低估的作用,肿瘤干细胞与它们的相互作用可能贯穿了肿瘤转移过程的始末.阐明转移肿瘤干细胞在肿瘤转移中的作用机制,将为肿瘤转移的靶向治疗提供理论依据.     

乳腺癌干细胞研究现状

肿瘤干细胞理论认为肿瘤可能是由肿瘤干细胞和其所处微环境产生,而肿瘤干细胞由正常干细胞突变而来.乳腺癌干细胞是第一个在实体瘤中被鉴定的肿瘤干细胞,人们采用多种策略成功分离出乳腺癌干细胞,对其生物学行为的认识正逐渐深入.乳腺癌干细胞的自我更新、分化等特性受到微环境和许多信号转导通路的调控.如何靶向治疗乳腺癌干细胞,最终根治乳腺癌,正逐渐成为肿瘤靶向治疗研究的一个热点.     

肿瘤干细胞相关研究进展

干细胞具有自我更新和多向分化的特征.随着对干细胞进一步了解及肿瘤基础研究的不断深入,越来越多证据表明肿瘤中极少数细胞具有干细胞特征,肿瘤干细胞概念随之产生,且已从血液肿瘤、乳腺癌及神经系统肿瘤中分离出肿瘤干细胞.这些细胞具有治疗抵抗特性,能够耐受传统的细胞毒化疗和放射治疗.肿瘤生长正是这些具有特殊表型细胞分化增殖的结果.许多学者认为,肿瘤复发、转移以及耐药等均与肿瘤干细胞相关,肿瘤治疗关键应该针对肿瘤干细胞.这一全新的治疗概念给肿瘤治疗带来希望,同时对传统肿瘤治疗模式提出了巨大挑战.肿瘤干细胞的发现、自身特点以及对肿瘤治疗可能影响的研究具有重要意义.     

肿瘤干细胞在肿瘤转移过程中的作用

肿瘤干细胞(NSC)是一种增殖特性失控可形成肿瘤的具有干细胞特性的细胞,在肿瘤转移中起重要作用,其作用机制贯穿于肿瘤发生、发展以及转归等过程中.     

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.     

肿瘤干细胞研究进展

利用特异性的细胞表面标记分子已经从各类肿瘤组织中分离到了肿瘤干细胞,包括骨髓瘤、肺癌、结肠癌、前列腺癌和胰腺癌.但存在细胞表面标记分子专属性差以及异种移植问题.从临床应用角度来看,将肿瘤干细胞作为肿瘤治疗的靶点,寻找肿瘤干细胞与肿瘤发生的密切关系,选择性地杀伤肿瘤干细胞,为临床根治肿瘤和防止肿瘤复发与转移提供了新的思路.     

Stem cell-like cancer cells in cancer cell lines

Both stem cells and cancer cells are thought to be capable of unlimited proliferation. Moreover, a small number of cancer cells express stem cell markers, including CD133 and ATP-binding cassette transporters, by which the cells can pump out specific fluorescence dyes, such as Hoechst33342, as well as anti-cancer drugs, suggesting that either cancer cells resemble stem cells or cancers contain stem cell-like cancer cells, called "cancer stem cells (CSCs)". Using the common characteristics of tissue-specific stem cells, it was demonstrated that many types of tumors and cancer cell lines contain CSCs, which self-renew, express stem cell markers, and are tumorigenic. It was also shown that CSCs are resistant to anti-cancer drugs and irradiation. Thus CSCs might be a crucial target for the therapy. Because tumors contain CSCs and recruited normal stem cells, both of which contribute to tumorigenesis, it is difficult to separate CSCs from tumors. By contrast, cancer cell lines do not have any contaminating normal stem cells that quickly loose mulitpotentiality and differentiate in normal culture condition, suggesting that cancer cell lines could be an attractive alternative source of cells for CSC research. In this review I summarize the recent progress in CSC research using cancer cell lines.     

Side population cells in human cancers

Cancer stem cells (CSCs) are found in multiple tumor types. While the presence of surface markers selectively expressed on CSCs are used to isolate these cells, no marker or pattern of makers are known to prospectively identify CSCs in many tumor types. In such cases exploitation of stem cell characteristics can be used to identify CSCs and one such characteristic is the capacity to extrude dyes such as Hoechst 33342. Cell that exclude this dye are referred to as side population (SP) cells. These cells share characteristics of CSCs, specifically, they are enriched for tumor initiating capacity, they express stem-like genes, and they are resistant to chemotherapeutic drugs. Dye exclusion is a valuable technique as it identifies a unique population of cells with stem-like characteristics.     

MicroRNA regulation of cancer stem cells

Cancer stem cells (CSC), or cancer cells with stem cell properties, have been reported in many human tumors and are thought to be responsible for tumor initiation, therapy resistance, progression, relapse, and metastasis. Despite their potential clinical importance, how CSCs are regulated at the molecular level is not well understood. MicroRNAs (miRNA), small noncoding RNAs that play critical roles in normal stem cell functions during development, have emerged as important regulators of CSCs as well. In this review, we summarize the current major findings of miRNA regulation of various CSCs and discuss our recent findings that miR-34a suppresses prostate CSCs and metastasis by directly repressing CD44. This recent progress has important implications for understanding how CSCs are intricately regulated by networks of miRNAs and for developing novel mechanism-based miRNA therapeutics that specifically target CSCs.     

Complexity of cancer stem cells

Heterogeneity of tumor tissue has been accounted for in recent years by a hierarchy‐based model in which cancer stem cells (CSCs) have the ability both to self‐renew and to give rise to differentiated tumor cells and are responsible for the overall organization of a tumor. Research into CSCs has progressed rapidly and concomitantly with recent advances in the biology of normal tissue stem cells, resulting in the identification of CSCs in a wide range of human tumors. Studies of mouse models of human cancer have provided further insight into the characteristics of CSCs as well as a basis for the development of novel therapies targeted to these cells. However, recent studies have revealed complexities, such as plasticity of stem cell properties and clonal diversity of CSCs, in certain tumor types that have led to revision of the original CSC model. In this review, we summarize the history of the discovery and characterization of CSCs, as well as address recent advances that have revealed the complexity of these cells and their therapeutic implications.     

肿瘤干细胞与microRNA的研究进展

肿瘤干细胞是肿瘤的起源性细胞, 具有高度的致瘤性和耐药性。微小RNA(microRNA或miRNA)是由21~25个核苷酸组成的内源性非编码单链RNA, 是基因表达调控因子, 参与许多生物功能的调节。最近的研究发现, microRNA参与肿瘤干细胞的分化、自我更新等生物学特性的调控。肿瘤干细胞和microRNAs可以作为肿瘤研究的一个新的切入点。本文就近年来的研究进展做简要综述。      

Prostate cancer stem cells and their potential roles in metastasis

Most solid tumors have now been reported to contain stem cell-like cells called cancer stem cells (CSCs). These cells are endowed with high tumorigenic capacity and may be the cells that drive tumor formation, maintain tumor homeostasis, and mediate tumor metastasis. Since these self-renewing cancer cells may be the sole population to develop a primary tumor, it is predicted that CSCs may also represent the lethal seeds of metastasis, as supported by a flurry of recent studies on the relationship between CSCs and metastasis. Herein, we summarize current knowledge of stem/progenitor cells and CSCs, especially in the context of normal human prostate and prostate cancer. We further update the recently gained knowledge on the involvement of CSCs in metastasis. We also discuss the fundamental influence of tumor microenvironment on the manifestation of CSCs and metastasis. Finally, we discuss the clinical implication of CSC-based therapy.     

Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways

Tumor relapse and metastasis remain major obstacles for improving overall cancer survival, which may be due at least in part to the existence of cancer stem cells (CSCs). CSCs are characterized by tumorigenic properties and the ability to self-renew, form differentiated progeny, and develop resistance to therapy. CSCs use many of the same signaling pathways that are found in normal stem cells, such as Wnt, Notch, and Hedgehog (Hh). The origin of CSCs is not fully understood, but data suggest that they originate from normal stem or progenitor cells, or possibly other cancer cells. Therapeutic targeting of both CSCs and bulk tumor populations may provide a strategy to suppress tumor regrowth. Development of agents that target critical steps in the Wnt, Notch, and Hh pathways will be complicated by signaling cross-talk. The role that embryonic signaling pathways play in the function of CSCs, the development of new anti-CSC therapeutic agents, and the complexity of potential CSC signaling cross-talk are described in this Review.     

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。     

To wake up cancer stem cells,or to let them sleep,that is the question

Cancer stem cells (CSCs) generate transient‐amplifying cells and thereby contribute to cancer propagation. A fuller understanding of the biological features of CSCs is expected to lead to the development of new anticancer therapies capable of eradicating this life‐threatening disease. Cancer stem cells are known to maintain a non‐proliferative state and to enter the cell cycle only infrequently. Given that conventional anticancer therapies preferentially target dividing cells, CSCs are resistant to such treatments, with those remaining after elimination of bulk cancer cells potentially giving rise to disease relapse and metastasis as they re‐enter the cell cycle after a period of latency. Targeting of the switch between quiescence and proliferation in CSCs is therefore a potential strategy for preventing the reinitiation of malignancy, underscoring the importance of elucidation of the mechanisms by which these cells are maintained in the quiescent state. The fundamental properties of CSCs are thought to be governed cooperatively by internal molecules and cues from the external microenvironment (stem cell niche). Several such intrinsic and extrinsic regulators are responsible for the control of cell cycle progression in CSCs. In this review, we address two opposite approaches to the therapeutic targeting of CSCs – wake‐up and hibernation therapies – that either promote or prevent the entry of CSCs into the cell cycle, respectively, and we discuss the potential advantages and risks of each strategy.     

肿瘤干细胞的临床意义

肿瘤干细胞(cancer stem cell, CSC)是近年来在许多肿瘤组织中发现的一类特殊干细胞。肿瘤干细胞具有自我更新和分化的能力,可以通过不断分化肿瘤细胞使新的肿瘤产生;肿瘤干细胞具有很强的耐药性和放射抗拒,这可以用来解释肿瘤的复发和转移。肿瘤干细胞可用于对肿瘤的诊断和治疗：通过对肿瘤干细胞标志物的鉴定可实现对一些肿瘤的早期诊断;一些新的治疗手段则通过作用于肿瘤干细胞的信号转导途径、表面标记和其生存的微环境,以及诱导其分化,从而达到靶向治疗肿瘤的目的。深入研究肿瘤干细胞的耐药性以及确定更多的肿瘤干细胞标志物,可为肿瘤治疗提供新途径。