肿瘤干细胞与肿瘤相关巨噬细胞的相互作用

肿瘤微环境(tumor microenvironment,TME)不仅促进了肿瘤的早期形成和远处转移,而且随着肿瘤的进展,其自身也不断地发生变化。作为TME的重要组成部分,肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)可通过分泌多种细胞因子激活IL-6/STAT3、TGF-β、Wnt/β-catenin等信号通路促进肿瘤干细胞(cancer stem cells,CSCs)的存活、自我更新和化疗耐药等。同时,CSCs也可通过分泌多种细胞因子和趋化因子等募集巨噬细胞,并将其诱导为TAMs重塑CSCs特定的生态位,维持CSCs表型并促进肿瘤进展。TAMs与CSCs的相互作用在促进肿瘤生长、转移及化疗耐药等方面发挥了重要作用。本文对TME中CSCs与TAMs相互作用的研究进行综述,并总结了以CSCs与TAMs相互作用为靶点在新型癌症治疗以及增强化疗效果等方面的重要潜力。     

肿瘤干细胞在肿瘤治疗中的研究进展

肿瘤干细胞(cancer stem cells,CSCs)学说的成熟发展和研究成为当前肿瘤治疗研究的热点之一,因其特殊的生物学特性在肿瘤防治中起重要作用。以CSCs为靶点为肿瘤治疗开辟了一条新思路。传统的治疗不能有效靶向CSC,开发针对CSC靶向治疗的新方法,将对肿瘤的耐药、复发、转移具有革新意义。     

人肿瘤干细胞异种移植模型进展

人肿瘤干细胞（human cancer stem cells,CSCs）分离后异种移植至模型内的成瘤特性,为研究肿瘤病因学和制订抗癌策略提供了新的手段和方法。但是,目前人肿瘤干细胞的鉴别离不开移植至异种免疫缺陷鼠内建立肿瘤干细胞的动物模型。本文主要从CSCs的概念、CSCs与肿瘤的关系、CSCs异种移植模型研究进展、模型建立的影响因素、模型建立存在的问题等进行简要综述,为异种移植模型的建立提供参考。     

肿瘤干细胞的光动力治疗研究进展

肿瘤干细胞(cancerstem cells,CSCs)是在肿瘤组织中具有干细胞特性的细胞亚群,它具有正常干细胞的多向分化潜能,能够无限增值和自主分化为各种具有异质性的肿瘤细胞。CSCs在肿瘤的发生、生长、转移中起着重要作用。同时,CSCs对目前大多数治疗如化疗、放疗不敏感,甚至具有耐药性,这也就导致了恶性肿瘤在治疗后容易复发。鉴于此,针对肿瘤干细胞的治疗日益受到关注,光动力疗法(photodynamictherapy,PDT)由于其微创性,不良反应少,靶向性强等特点在肿瘤的治疗研究中不断得到发展。本文将从CSCs的特性入手,结合PDT治疗的最新进展,探讨PDT治疗在肿瘤干细胞治疗中的应用。     

肿瘤干细胞对恶性肿瘤辅助治疗的影响

放化疗是目前恶性肿瘤治疗的重要手段,但是迄今为止,除了手术以外,几乎没有能单独根治恶性肿瘤的治疗方法,甚至一些恶性肿瘤在手术、化疗或放疗后会出现再生和侵袭能力增强,被称为恶性肿瘤治疗后再增殖,这可能是恶性肿瘤治疗失败的主要原因,其主要机制可能是肿瘤干细胞(cancer stem cells,CSCs)对放化疗的耐受,以及放化疗导致肿瘤细胞的上皮细胞间质化,继而提高了肿瘤侵袭性。该文将从CSCs的角度重新探讨放化疗等辅助治疗对恶性肿瘤的影响。     

微小RNA与肿瘤干细胞耐药的研究进展

肿瘤干细胞（Cancer stem cells,CSCs）是肿瘤组织中一小部分具有自我更新和致瘤性的细胞,具有特殊的耐药机制,与肿瘤的复发和治疗失败关系密切。微小RNA（microRNAs,miRNAs）是一类长度约为19～25个核苷酸的内源性非编码单链RNA,能够通过调控相关靶基因的表达,参与调控肿瘤干细胞增殖、凋亡、上皮-间质转化等重要的生命过程,引起CSCs对化疗药物产生原发性多药耐药性。本论文就miRNAs在调控CSCs多药耐药性方面的研究进展作一综述。     

表观遗传学与肿瘤干细胞

肿瘤干细胞模型是关于肿瘤形成及生物学特征的一种重要观点。该模型认为肿瘤发生的核心是一群类似于成体干细胞的肿瘤细胞, 具有自我增殖和分化潜能, 称为肿瘤干细胞(Cancer stem cells, CSCs)。目前在多种肿瘤中都发现了CSCs, 其不仅能导致肿瘤发生, 还是引起肿瘤转移、复发、抗药的关键原因。因此, 研究CSC的调控机制具有重要意义。近年来的研究发现, 除了基础的遗传学因素外, 表观遗传学在CSCs的调控中同样具有重要作用。目前主要的表观遗传学机制包括DNA甲基化、组蛋白修饰、染色质重塑及miRNA等, 能有效调节基因表达及细胞表型, 也是肿瘤研究的新热点。文章主要围绕近几年CSCs的特性研究及表观遗传学线索, 阐述表观遗传学机制调控CSCs的最新进展。     

肿瘤干细胞研究进展

肿瘤干细胞（cancer stem cell, CSC）假说是近年来提出的关于肿瘤发生的新理论,在所有的肿瘤细胞中,可能只有一小部分细胞具有产生肿瘤并维持肿瘤生长和异质性的能力,目前已经在白血病、乳腺癌、脑癌等肿瘤组织中成功分离出了肿瘤干细胞,深入了解肿瘤干细胞的生物学特性、发展相应的鉴别方法以及特殊的治疗手段对癌症的临床治疗有着重要的意义。主要从肿瘤干细胞的概念、起源、鉴定分离方法、与正常干细胞的比较、比率以及与肿瘤转移的关系等方面进行了综述。     

CD133分子与造血干/祖细胞和癌干细胞之间的关系

越来越多的实体瘤癌干细胞(CSCs)研究中鉴定分离出含有CD133+的CSCs亚群。深入了解CD133+分子的生物学特性及在细胞与肿瘤信号转导、药物耐受和放化疗抵抗等的相关性,将有助于靶向治疗CSCs。本文就CD133分子与造血干/祖细胞(HSPC)和CSCs之间的关系及其耐药机制的研究进展作一综述。     

c-kit~+心脏干细胞在心脏再生修复中的应用

心血管疾病的流行是一个全球性的现象,在我国,其患病率也不断增长。目前尚无有效的治疗方法以解决心肌细胞损失这一关键问题,而干细胞移植很可能成为新的治疗方法。C-kit+心脏干细胞(cardiac stem/progenitor cell,CSCs)的发现证实了CSCs的存在,并为心脏的再生和修复治疗带来了新的曙光。C-kit+CSCs在心肌梗死、心力衰竭等心脏疾病中的作用得到了多项体内外实验及临床试验的证实,但由于目前尚缺乏直接的充分的证据证明内源性或外源性的c-kit+CSCs可分化为相当数量的成熟的具有功能的心肌细胞,其治疗机制尚存争议,同时,将其应用于临床仍面临多个问题。     

肿瘤干细胞与肿瘤转移

近年来,肿瘤干细胞(cancer stem cell,CSC)学说研究认为CSC与肿瘤发生、发展、转移和复发关系极为密切。研究还发现CSC具有明显的异质性,即CSC可分为增生、耐药、侵袭和转移等行为不同的亚群细胞,其中具有转移生物学特性的CSC亚群细胞称为肿瘤转移干细胞(migrating cancer stem cell,MCSC)。目前认为,上皮-间质转变、趋化因子和靶器官微环境可能在肿瘤转移过程中起着重要作用。针对MCSC及其相关机制的靶向治疗有望能更有效地遏制肿瘤的转移。     

The stem cell hypothesis in head and neck cancer

Cancer stem cells (CSCs) are tumoral cells which have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. In the last 10 years the pathological meaning and the existence of CSCs have been matter of discussion and a large number of articles have been published about the role that these cells play in the development and maintenance of the tumors. Head and neck squamous-cell carcinoma (HNSCC) is the sixth most common cancer worldwide: early diagnosis of high-risk premalignant lesions are high priorities for reducing deaths due to head and neck cancer. In the last years the CSCs hypothesis has been faced also for head and neck cancer, with the aim of a better comprehension of the tumor biology and an early diagnosis. The evidence that the development of a tumor comes from a small number of cells with stem-like characteristic, could bring too to the identification of therapies against these cellular target, fundamental for maintenance and progression of the lesion. Here, a literature review has been reported about the detection of supposed CSCs in head and neck cancer.     

Using ABCG2-molecule-expressing side population cells to identify cancer stem-like cells in a human ovarian cell line

CSCs (cancer stem cells) are a small subset of cells within a tumour that possesses the characteristics of stem cells and are considered to be responsible for resistance to chemoradiation. Identification of CSCs through stem cell characteristics might have relevant clinical implications. In this study, SP (side population ) cells were sorted from a human ovarian cancer cell line by FACS to determine whether cancer stem cell-like SP cells were present. A very small fraction of SP cells (2.6%) was detected in A2780 cells. SP cells possessed the following characteristics: highly proliferative activity, marked ability for self-renewal in soft agar and culture medium, high expression of ABCG2, drug resistance to vinblastine in vitro, and strong tumourigenic potential in Balb/c nude mice. It is concluded that there exists in the A2780 cell line a small number of SP cells with high expression of ABCG2. The cells have the characteristics of cancer stem-like cells, and identification and cloning of such human SP cells can help in improving therapeutic approaches to ovarian cancer in patients.     

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines

Cancer stem cells (CSCs) are defined as a subset of slow cycling and undifferentiated cells that divide asymmetrically to generate highly proliferative, invasive, and chemoresistant tumor cells. Therefore, CSCs are an attractive population of cells to target therapeutically. CSCs are predicted to contribute to a number of types of malignancies including those in the blood, brain, lung, gastrointestinal tract, prostate, and ovary. Isolating and enriching a tumor cell population for CSCs will enable researchers to study the properties, genetics, and therapeutic response of CSCs. We generated a protocol that reproducibly enriches for ovarian cancer CSCs from ovarian cancer cell lines (SKOV3 and OVCA429). Cell lines are treated with 20 µM cisplatin for 3 days. Surviving cells are isolated and cultured in a serum-free stem cell media containing cytokines and growth factors. We demonstrate an enrichment of these purified CSCs by analyzing the isolated cells for known stem cell markers Oct4, Nanog, and Prom1 (CD133) and cell surface expression of CD177 and CD133. The CSCs exhibit increased chemoresistance. This method for isolation of CSCs is a useful tool for studying the role of CSCs in chemoresistance and tumor relapse.     

Emerging role of exosome signalling in maintaining cancer stem cell dynamic equilibrium

Cancer stem cells (CSCs) are a small subset of heterogeneous cells existed in tumour tissues or cancer cell lines with self‐renewal and differentiation potentials. CSCs were considered to be responsible for the failure of conventional therapy and tumour recurrence. However, CSCs are not a static cell population, CSCs and non‐CSCs are maintained in dynamic interconversion state by their self‐differentiation and dedifferentiation. Therefore, targeting CSCs for cancer therapy is still not enough,exploring the mechanism of dynamic interconversion between CSCs and non‐CSCs and blocking the interconversion seems to be imperative. Exosomes are 30‐100 nm size in diameter extracellular vesicles (EVs) secreted by multiple living cells into the extracellular space. They contain cell‐state‐specific bioactive materials, including DNA, mRNA, ncRNA, proteins, lipids, etc. with their specific surface markers, such as, CD63, CD81, Alix, Tsg101, etc. Exosomes have been considered as information carriers in cell communication between cancer cells and non‐cancer cells, which affect gene expressions and cellular signalling pathways of recipient cells by delivering their contents. Now that exosomes acted as information carriers, whether they played role in maintaining dynamic equilibrium state between CSCs and non‐CSCs and their mechanism of activity are unknown. This review summarized the current research advance of exosomes’ role in maintaining CSC dynamic interconversion state and their possible mechanism of action, which will provide a better understanding the contribution of exosomes to dedifferentiation and stemness acquisition of non‐CSCs, and highlight that exosomes might be taken as the attractive target approaches for cancer therapeutics.     

胃癌干细胞研究进展

胃癌是仅次于肺癌的第二大致死率癌症,尽管近年来对胃癌研究有了很大进展,但由于缺乏良好的动物模型,对胃癌的发病机理仍然不是很清楚.近年的研究表明,肿瘤组织不是由均一细胞构成的,其中存在一些少量细胞可以自我更新并可以分化为肿瘤组织的其他细胞,这类细胞具有类似成体组织干细胞（tissue stem cells）的特性称之为肿瘤干细胞（cancer stem cells）.肿瘤干细胞被认为在肿瘤的生长、转移、复发中发挥着重要作用.有证据表明在胃癌组织中存在胃癌干细胞（gastric cancer stem cells）,但是对胃癌干细胞的来源仍然不是十分明确.对肿瘤干细胞的研究有助于癌症的治疗,改变目前药物针对所有癌细胞的治疗策略.     

Quiescent stem cells in intestinal homeostasis and cancer

Abstract

Adult stem cell niches are characterized by a dichotomy of cycling and quiescent stem cells: while the former are responsible for tissue turnover, their quiescent counterparts are thought to become active upon tissue injury thus underlying the regenerative response. Moreover, quiescence prevents adult stem cells from accumulating mutations thus ensuring a reservoir of unaltered stem cells. In the intestine, while cycling stem cells were shown to give rise to the main differentiated lineages, the identity of their quiescent equivalents remains to date elusive. This is of relevance for conditions such as Crohn's disease and ulcerative colitis where quiescent stem cells may underlie metaplasia and the increased cancer risk associated with chronic inflammation. Tumours are thought to share a comparable hierarchical structure of adult tissues with pluripotent and self-renewing cancer stem cells (CSCs) giving rise to more differentiated cellular types. As such, neoplastic lesions may encompass both cycling and quiescent CSCs. Because of their infrequent cycling, quiescent CSCs are refractory to chemo- and radiotherapy and are likely to play a role in tumour dissemination, dormancy and recurrence.     

Proteomic analysis of cancer stem cells in human prostate cancer cells

Results from recent studies support the hypothesis that cancer stem cells (CSCs) are responsible for tumor initiation and formation. Here, we applied a proteome profiling approach to investigate the mechanisms of CSCs and to identify potential biomarkers in the prostate cancer cell line DU145. Using MACS, the DU145 prostate cancer cell line was isolated into CD44+ or CD44− cells. In sphere culture, CD44+ cells possessed stem cell characteristics and highly expressed genes known to be important in stem cell maintenance. In addition, they showed strong tumorigenic potential in the clonogenic assay and soft agar colony formation assay. We then analyzed and identified proteins that were differentially expressed between CD44+ and CD44− using two-dimensional gel electrophoresis and LC-MS/MS. Cofilin and Annexin A5, which are associated with proliferation or metastasis in cancer, were found to be positively correlated with CD44 expression. These results provide information that will be important to the development of new cancer diagnostic tools and understanding the mechanisms of CSCs although a more detailed study is necessary to investigate the roles of Cofilin and Annexin A5 in CSCs.     

The malignant social network: Cell-cell adhesion and communication in cancer stem cells

Tumors contain a vastly complicated cellular network that relies on local communication to execute malignant programs. The molecular cues that are involved in cell-cell adhesion orchestrate large-scale tumor behaviors such as proliferation and invasion. We have recently begun to appreciate that many tumors contain a high degree of cellular heterogeneity and are organized in a cellular hierarchy, with a cancer stem cell (CSC) population identified at the apex in multiple cancer types. CSCs reside in unique microenvironments or niches that are responsible for directing their behavior through cellular interactions between CSCs and stromal cells, generating a malignant social network. Identifying cell-cell adhesion mechanisms in this network has implications for the basic understanding of tumorigenesis and the development of more effective therapies. In this review, we will discuss our current understanding of cell-cell adhesion mechanisms used by CSCs and how these local interactions have global consequences for tumor biology.