Stem cells: the intestinal stem cell as a paradigm

Stem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems will result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones. Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.     

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.     

Normal stem cells and cancer stem cells: the niche matters

Scientists have tried for decades to understand cancer development in the context of therapeutic strategies. The realization that cancers may rely on "cancer stem cells" that share the self-renewal feature of normal stem cells has changed the perspective with regard to new approaches for treating the disease. In this review, we propose that one of the differences between normal stem cells and cancer stem cells is their degree of dependence on the stem cell niche, a specialized microenvironment in which stem cells reside. The stem cell niche in adult somatic tissues plays an essential role in maintaining stem cells or preventing tumorigenesis by providing primarily inhibitory signals for both proliferation and differentiation. However, the niche also provides transient signals for stem cell division to support ongoing tissue regeneration. The balance between proliferation-inhibiting and proliferation-promoting signals is the key to homeostatic regulation of stem cell maintenance versus tissue regeneration. Loss of the niche can lead to loss of stem cells, indicating the reliance of stem cells on niche signals. Therefore, cancer stem cells may arise from an intrinsic mutation, leading to self-sufficient cell proliferation, and/or may also involve deregulation or alteration of the niche by dominant proliferation-promoting signals. Furthermore, the molecular machinery used by normal stem cells for homing to or mobilizing from the niche may be "hijacked" by cancer stem cells for invasion and metastasis. We hope this examination of the interaction between stem cells and their niche will enhance understanding of the process of cancer development, invasiveness, and metastasis and reveal possible targets for cancer treatment.     

Normal stem cells and cancer stem cells: similar and different

The functional capabilities of normal stem cells and tumorigenic cancer cells are conceptually similar in that both cell types are able to proliferate extensively. Indeed, mechanisms that regulate the defining property of normal stem cells – self-renewal – also frequently mediate oncogenesis. These conceptual links are strengthened by observations in some cancers that tumorigenic cells can not only renew their malignant potential but also generate bulk populations of non-tumorigenic cells in a manner that parallels the development of differentiated progeny from normal stem cells. But cancer cells are not normal. Although tumorigenic cells and normal stem cells are similar in some ways, they are also fundamentally different in other ways. Understanding both shared and distinguishing mechanisms that regulate normal stem cell proliferation and tumor propagation is likely to reveal opportunities for improving the treatment of patients with cancer.     

Stem cells: an autonomous cell producing system

Stem cells have been traditionally considered to be a reserve population, in which the primary control is the rate of differentiation. Alterations in proliferation rate are then considered to be the results of changes in the number of stem cells. This article suggests that perhaps the reverse is true, namely that the rate of stem cell production is primarily controlled, and not the number of stem cells.     

Stem cells of ependymoma

Ependymomas are tumours that arise throughout the central nervous system. Little is known regarding the aberrant cellular and molecular processes that generate these tumours.[第一段]     

Stem cells of ependymoma

Ependymomas are tumours that arise throughout the central nervous system. Little is known regarding the aberrant cellular and molecular processes that generate these tumours. This lack of knowledge has hampered efforts to reduce the significant mortality and morbidity that are associated with ependymoma. Here, we review recent data that suggest that radial glia are cells of origin of ependymoma, and discuss the processes that might transform these neural progenitors into ependymoma cancer stem cells.     

Stem cells and proteomics

With the accomplishment of the draft of human genome project and the sequencing of several decades of organisms and the adventure of post-genomics, proteomics, an important subject of post-genomics, has been applied in many fields such as biology, oncology and medicine, etc. People’s attention has gradually transferred from revealing the genetic information to discovering the functions of the genetic materials. In consideration of the limited number of genes and the relative stability of thei…     

Stem cells and cancer

The cell of origin of cancer has been a strongly debated topic through out the history of cancer research. This review provides a historic framework and a synopsis of how the theories of cancer initiation and progression evolved from early times to the present day. We present the concept of a cancer stem cell, and review for you the literature supporting the existence of cancer stem cells in addition to a brief discussion on our own work supporting a bone marrow-derived source for the cancer stem cell, as well as cells of the cancer stroma.     

干细胞与肿瘤发生

干细胞具有自我更新及多向分化能力,可以分化成机体组织器官的各种成熟细胞。人们发现许多肿瘤的发生都与成体干细胞有着密切的关系,肿瘤细胞可来源于成体干细胞积累的突变,因为干细胞具有无限增殖能力,在体内可长期存在,这使突变更容易在成体干细胞中发生和积累;肿瘤细胞也可来源于成体干细胞下游祖细胞积累的突变。随着研究深入还发现,肿瘤细胞与成体干细胞之间有着惊人的相似性——相似的生长调控机制和等级现象,由此提出了肿瘤干细胞的概念,并归纳了随机制论和等级理论解释为什么并非每个肿瘤细胞都具有再生肿瘤和转移的能力,许多文献更倾向于等级理论在起作用。目前已经在白血病和一些实体瘤中分离鉴定出肿瘤干细胞,在一些长期培养的肿瘤细胞系中也发现了类似的肿瘤干细胞。这些肿瘤干细胞具有自我更新能力和正常成体干细胞的一些耐药机制,对现有的抗肿瘤治疗不敏感,常导致肿瘤的复发和转移。因此,肿瘤干细胞的根除和检测对于肿瘤的治疗和预后评估都有重要的意义。     

Urothelial carcinoma: Stem cells on the edge

Tumors are heterogeneous collections of cells with highly variable abilities to survive, grow, and metastasize. This variability likely stems from epigenetic and genetic influences, either stochastic or hardwired by cell type-specific lineage programs. That differentiation underlies tumor cell heterogeneity was elegantly demonstrated in hematopoietic tumors, in which rare primitive cells (cancer stem cells (CSCs)) resembling normal hematopoietic stem cells are ultimately responsible for tumor growth and viability. Because of the compelling clinical implications CSCs pose—across the entire spectrum of cancers—investigators applied the CSC model to cancers arising in tissues with crudely understood differentiation programs. Instead of relying on differentiation, these studies used empirically selected markers and statistical arguments to identify CSCs. The empirical approach has stimulated important questions about “stemness” in cancer cells as well as the validity and stoichiometry of CSC assays. The recent identification of urothelial differentiation programs in urothelial carcinomas (UroCas) supports the idea that solid epithelial cancers (carcinomas) develop and differentiate analogously to normal epithelia and provides new insights about the spatial localization and molecular makeup of carcinoma CSCs. Importantly, CSCs from invasive UroCas (UroCSCs) appear well situated to exchange important signals with adjacent stroma, to escape immune surveillance, and to survive cytotoxic therapy. These signals have potential roles in treatment resistance and many participate in druggable cellular pathways. In this review, we discuss the implications of these findings in understanding CSCs and in better understanding how UroCas form, progress, and should be treated.     

神经干细胞和脑肿瘤干细胞研究进展

神经干细胞（NSC）是中枢神经系统（CNS）内具有自我更新和多向分化潜能的干细胞，主要存在于脑室下区域（SVZ），NSC通过自我更新和分化维持正常CNS的形态和功能。可塑性（plasticity）是NSC的重要特征，由NSC所处的微环境（microenvironment）决定。脑肿瘤干细胞（BTSC）是脑肿瘤中与NSC相似的细胞，是脑肿瘤发生和生长的细胞来源。BTSC可能起源于NSC，是NSC可塑性的表现，导致NSC向BTSC分化的机制可能是微环境作用的结果。     

肝干细胞与肝癌干细胞

正常肝干细胞在致癌因素作用下发生基因突变，获得无限增殖能力成为肿瘤干细胞，肿瘤干细胞分化成各种分化等级、表型不一的肿瘤。在正常肝干细胞转化成肝癌干细胞的过程中保留了一些干细胞表型特征和进一步向相对成熟细胞分化的能力。正常肝干细胞是肝癌重要起源。     

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.     

神经干细胞和脑肿瘤干细胞研究进展

神经干细胞(NSC)是中枢神经系统(CNS)内具有自我更新和多向分化潜能的干细胞,主要存在于脑室下区域(SVZ),NSC通过自我更新和分化维持正常CNS的形态和功能。可塑性(plastici- ty)是NSC的重要特征,由NSC所处的微环境(microenvironment)决定。脑肿瘤干细胞(BTSC)是脑肿瘤中与NSC相似的细胞,是脑肿瘤发生和生长的细胞来源。BTSC可能起源于NSC,是NSC可塑性的表现,导致NSC向BTSC分化的机制可能是微环境作用的结果。     

Control of stress signaling in stem cells: crossroads of stem cells and cancer

Tumorigenesis is a relatively rare event in the human body considering the enormous number of cells composing our body and the frequent occurrence of genetic mutations in each cell. Nevertheless, the cells that happen to meet the minimum requirements can be transformed when stressed by a variety of oncogenic stimulations, then progress to form tumors. The vigorous competition between oncogenic signaling and tumor-suppressor defense is a critical determinant of cellular fate, which can be either tumorigenic transformation or cellular senescence/apoptosis depending on “who wins the battle.” Recently, a number of cancers have been reported to originate from stem cells, whose self-renewing properties are normally reduced by innate tumor suppressors. Therefore, exploring the innate mechanism by which stem cells modulate tumor suppressors to maintain their “stemness” may provide valuable clues to characterize the distinctive oncogenic susceptibility of stem cells. This review is focused on the recent advances in the field of tumorigenesis of stem cells and on the associated molecular mechanisms.