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1.
Stem cells and cancer are inextricably linked; the process of carcinogenesis initially affects normal stem cells or their
closely related progenitors and then, at some point, neoplastic stem cells are generated that propagate and ultimately maintain
the process. Many, if not all, cancers contain a minority population of self-renewing stem cells, “cancer stem cells”, that
are entirely responsible for sustaining the tumour and for giving rise to proliferating but progressively differentiating
cells that contribute to the cellular heterogeneity typical of many solid tumours. Thus, the bulk of the tumour is often not
the clinical problem, and so the identification of cancer stem cells and the factors that regulate their behaviour are likely
to have an enormous bearing on the way that we treat neoplastic disease in the future. This review summarises (1) our knowledge
of the origins of some cancers from normal stem cells and (2) the evidence for the existence of cancer stem cells; it also
illustrates some of the stem cell renewal pathways that are frequently aberrant in cancer and that may represent druggable
targets. 相似文献
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Hirai H 《Human cell》2002,15(4):190-198
Stem cells have been defined as clonogenic cells that undergo both self-renewal and differentiation to more committed progenitors and functionally specialized mature cells. Of late years, stem cells have been identified in a variety of tissues of an adult body. Depending on the source, they have the potential to form one or more, or even all cell types of an organism. Stem cell research provided some outstanding contributions to our understanding of developmental biology and offered much hope for cell replacement therapies overcoming a variety of diseases. The establishment of human ES cell lines enabled us to generate all tissues we comprise. Recently, excitement has been evoked by the controversial evidence that adult stem cells have a much higher degree of developmental plasticity than previously imagined. More recently, the existence of multipotent somatic stem cells in bone marrow has been reported. Combined with these discoveries and achievements as well as the developing technologies, scientists are now trying to bring stem cell therapies to the clinic. 相似文献
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Differentiation profile of brain tumor stem cells: a comparative study with neural stem cells 总被引:25,自引:0,他引:25
Understanding of the differentiation profile of brain tumor stem cells (BTSCs), the key ones among tumor cell population, through comparison with neural stem cells (NSCs) would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD 133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and β-tubulinlII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma. 相似文献
5.
Primary malignant tumors of the spine are relatively rare, less than 5% of all spinal column tumors. However, these lesions are often among the most difficult to treat and encompass challenging pathologies such as chordoma and a variety of invasive sarcomas. The mechanisms of tumor recurrence after surgical intervention, as well as resistance to radiation and chemotherapy, remain a pervasive and costly problem. Recent evidence has emerged supporting the hypothesis that solid tumors contain a sub-population of cancer cells that possess characteristics normally associated with stem cells. Particularly, the potential for long-term proliferation appears to be restricted to subpopulations of cancer stem cells(CSCs) functionally defined by their capacity to self-renew and give rise to differentiated cells that phenotypically recapitulate the original tumor, thereby causing relapse and patient death. These cancer stem cells present a unique opportunity to better understand the biology of solid tumors in general, as well as targets for future therapeutics. The general objective of the current study is to discuss the fundamental concepts for understanding the role of CSCs with respect to chemoresistance, radioresistance, special cell surface markers, cancer recurrence and metastasis intumors of the osseous spine. This discussion is followed by a specific review of what is known about the role of CSCs in chordoma, the most common primary malignant osseous tumor of the spine. 相似文献
6.
Primary malignant tumors of the spine are relatively rare, less than 5% of all spinal column tumors. However, these lesions are often among the most difficult to treat and encompass challenging pathologies such as chordoma and a variety of invasive sarcomas. The mechanisms of tumor recurrence after surgical intervention, as well as resistance to radiation and chemotherapy, remain a pervasive and costly problem. Recent evidence has emerged supporting the hypothesis that solid tumors contain a sub-population of cancer cells that possess characteristics normally associated with stem cells. Particularly, the potential for long-term proliferation appears to be restricted to subpopulations of cancer stem cells (CSCs) functionally defined by their capacity to self-renew and give rise to differentiated cells that phenotypically recapitulate the original tumor, thereby causing relapse and patient death. These cancer stem cells present a unique opportunity to better understand the biology of solid tumors in general, as well as targets for future therapeutics. The general objective of the current study is to discuss the fundamental concepts for understanding the role of CSCs with respect to chemoresistance, radioresistance, special cell surface markers, cancer recurrence and metastasis in tumors of the osseous spine. This discussion is followed by a specific review of what is known about the role of CSCs in chordoma, the most common primary malignant osseous tumor of the spine. 相似文献
7.
The identification of brain tumor stem cells (BTSCs) leads to promising progress on brain tumor treatment. For some brain
tumors, BTSCs are the driving force of tumor growth and the culprits that make tumor revive and resistant to radiotherapy
and chemotherapy. Therefore, it is specifically significant to eliminate BTSCs for treatment of brain tumors. There are considerable
similarities between BTSCs and normal neural stem cells (NSCs), and diverse aspects of BTSCs have been studied to find potential
targets that can be manipulated to specifically eradicate BTSCs without damaging normal NSCs, including their surface makers,
surrounding niche, and aberrant signaling pathways. Many strategies have been designed to kill BTSCs, and some of them have
reached, or are approaching, effective therapeutic results. Here, we will focus on advantages in the issue of BTSCs and emphasize
on potential therapeutic strategies targeting BTSCs. 相似文献
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Doherty RE Haywood-Small SL Sisley K Cross NA 《Biochemical and biophysical research communications》2011,414(4):801-807
Aldehyde dehydrogenase 1 (ALDH) activity is considered to be a marker of cancer stem cells (CSCs) in many tumour models, since these cells are more proliferative and tumourigenic than ALDHLo cells in experimental models. However it is unclear whether all CSC-like cells are within the ALDHHi population, or whether all ALDHHi cells are highly proliferative and tumourigenic. The ability to establish a stem cell hierarchy in vitro, whereby sub-populations of cells have differing proliferative and differentiation capacities, is an alternate indication of the presence of stem cell-like populations within cell lines. In this study, we have examined the interaction between ALDH status and the ability to establish a stem cell hierarchy in PC3 prostate cancer cells. We demonstrate that PC3 cells contain a stem cell hierarchy, and isolation of ALDHHi cells enriches for the most primitive holoclone population, however holoclone formation is not restricted to ALDHHi cells. In addition, we show that ALDH activity undergoes phenotypic plasticity, since the ALDHLo population can develop ALDHHi populations comparable to parental cells within 2 weeks in culture. Furthermore, we show that the majority of ALDHHi cells are found within the least primitive paraclone population, which is circumvented by culturing PC3 cells as spheroids in defined medium favouring stem cell characteristics. Although ALDHHi status enriches for holoclone formation, this activity may be mediated by a minority of ALDHHi cells. 相似文献
10.
Minal Garg 《World journal of stem cells》2012,4(7):62-70
This review discusses the various regulatory charac-teristics of microRNAs that are capable of generating widespread changes in gene expression via post translational repression of many mRNA targets and control self-renewal, differentiation and division of cells. It controls the stem cell functions by controlling a wide range of pathological and physiological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis and metastasis. Through either mRNA cleavage or translational repression, miRNAs alter the expression of their cognate target genes; thereby modulating cellular pathways that affect the normal functions of stem cells, turning them into cancer stem cells, a likely cause of relapse in cancer patients. This present review further emphasizes the recent discoveries on the functional analysis of miRNAs in cancer metastasis and implications on miRNA based therapy using miRNA replacement or anti-miRNA technologies in specific cancer stem cells that are required to establish their efficacy in controlling tumorigenic potential and safe therapeutics. 相似文献
11.
Emerging evidence points to the existence of pancreatic cancer stem cells (CSC) as the culprit in the initiation, maintenance, metastasis, and treatment resistance of pancreatic cancer. The existence of such a cell population would have an important impact on the design of novel therapies against this devastating disease. However, no in vivo validation or rebuttal of the pancreatic CSC hypothesis exists. Major backlashes in the discussion on CSC are firstly, the confusion between the terms CSC and cell of origin of pancreatic ductal adenocarcinoma (PDAC), secondly the ambiguity of the cell of origin itself and thirdly, the fact that the CSC hypothesis is based on cell sorting and xenografting experiments; the latter of which often precludes solid conclusions because of the lack of a natural microenvironment and differences in drug delivery. Nonetheless, recent studies in other cancers partially support the CSC hypothesis by demonstrating a link between epithelial-to-mesenchymal transdifferentiation/transition (EMT) and CSC properties. Such a link is again open to dispute as EMT is a reversible process which is highly dependent on major oncogenic pathways in PDAC [e.g. K-Ras, transforming growth factor-β (TGF-β)] rather than on presumed cancer stem cell pathways. Hence, the available evidence does not robustly support the CSC concept in PDAC and a thorough validation of this hypothesis in well-defined genetically engineered mouse models of pancreatic cancer is required. 相似文献
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Jiabo Di Tjitske Duiveman-de Boer Carl G Figdor Ruurd Torensma 《World journal of stem cells》2013,5(4):149-162
Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. However, in a large proportion of the patients the tumor grows back within a few years. Cancer stem cells, that are less responsive to these treatments, are blamed for this recurrence of disease. Immune therapy either cellular or humoral is a novel concept to treat cancer. It is based on the notice that immune cells invade the tumor. However, the tumor invest heavily to escape from immune elimination by recruiting several immune suppressive mechanisms. These processes are normally in place to limit excessive immune activation and prevent autoimmune phenomena. Here, we discuss current knowledge about the immune (suppressive) status in ovarian cancer. Moreover, we discuss the immunological targets of ovarian cancer stem cells. 相似文献
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Hsi-Lung Hsieh Ming-Chin Yu Li-Ching Cheng Ta-Sen Yeh Ming-Ming Tsai 《World journal of stem cells》2022,14(1):76-91
Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major reason for resistance to anticancer treatment(chemotherapy or radiotherapy),and for the development of tumor recurrence,epithelial–mesenchymal transition,and metastases.Additionally,GCSCs have the capacity for self-renewal,differentiation,and tumor initiation.They also synthesize antiapoptotic factors,demonstrate higher performance of drug efflux pumps,and display cell plasticity abilities.Moreover,the tumor microenvironment(TME;tumor niche)that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor.However,the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential.In this review,we provide up-todate information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development.This information will support improved diagnosis,novel therapeutic approaches,and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy.To date,most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents.However,when used in combination with adjuvant therapy,treatment can improve.By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC,the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy,radiotherapy,or other adjuvant treatment. 相似文献
15.
关于恶性肿瘤发生、复发与转移机制的研究由来已久,但目前的临床治疗方法依然不能克服肿瘤复发与转移的难题,肿瘤患者的生存率并未得到显著改善。近年来的研究提示肿瘤的起源、复发与转移的真正原因可能是存在于肿瘤内的极少数具有干细胞特性的细胞,即肿瘤干细胞(cancer stem cells,CSC)。与此同时,越来越多的研究表明,对于肿瘤干细胞的发生与功能维持,表观遗传学的调控机制可能发挥着极其重要的作用。该文简要综述目前肿瘤干细胞和表观遗传学相关领域的研究进展,并对肿瘤干细胞形成及发展过程中表观遗传学的调控作用及机制进行重点介绍。 相似文献
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Ikeda T 《Cell and tissue research》2008,331(1):263-269
Recent advances in regenerative medicine and in our understanding of neurogenesis may lead to new ways of recovering neuronal
function lost or damaged during the perinatal period; such injuries are not amenable to conventional therapies. We review
recent experimental studies based on immature rodental models of neonatal brain injury, especially hypoxic-ischemic encephalopathy.
The developing brain is revealed to have considerable potential with respect to proliferation and migration to the injured
site. However, the generation of fully differentiated neurons is extremely limited after brain injuries. Aggressive efforts
to adjust the environment of the damaged brain in which tissue regeneration is occurring or more cautious stem cell transplantation
will be required for the successful treatment of developmental brain injury.
This work was supported by a Research Grant for Cardiovascular Diseases (18C-1) from the Ministry of Health, Labour and Welfare. 相似文献
19.
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. 相似文献
20.
Xiaochun Sun Hua Cai Hui Qian Wei Zhu Yongmin Yan Huaxi Xu Wenrong Xu 《Cell biology international》2011,35(2):119-123
In the present study, MSCs (mesenchymal stem cells) were successfully isolated and identified from hUCC (human uterine cervix cancer) tissues. The morphological appearance, immunophenotype, growth curve, cell cycle, cytogenetic features and differentiation potential of these cells were investigated. Results showed that cells isolated from the uterine cervix cancer tissues displayed fibroblast‐like morphology and grew into colonies. Immunophenotyping by flow cytometry revealed that the isolated cells were positive for CD13, CD29, CD44, CD105 and HLA‐I, while negative for CD10, CD14, CD31, CD34, CD38 and HLA‐DR. The cells kept a normal karyotype by chromosome analysis. At the third passage, the percentages of cells in G0‐/G1‐, 2‐/M‐ and S‐phase were 84.94, 8.36 and 6.71%, respectively. Under appropriate induction conditions, these cells can differentiate into osteogenic, adipogenic cells and hepatocytes. Taken together, MSCs were confirmed to exist in hUCC tissues, which may provide a new target for clinical cancer therapy. 相似文献