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Results for “Cancer stem cells”

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At least 199 records · Page 11Linked to original sources
PubMed2006

Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins.

While polyploidy, a state of having fully duplicated sets of chromosomes per cell, has been described in normally developing bone marrow megakaryocytes or as an adaptive response in other cell types, aneuploidy is never detected in normal cells. Tetraploidy or aneuploidy can be induced by several signals and it is highly prevalent in different forms of cancers, suggesting a role for this cell cycle state in promoting cellular transformation. Investigations suggested that loss of heterozygosity of cancer-related genes in stem cells might contribute to genetic instability in progeny cells and to subsequent cancer development. Deregulated expression of chromosome passenger proteins, such as Aurora kinases or Survivin, is a hallmark of various cancers, and experimentally induced changes in these regulators can promote tetraploidy or aneuploidy and loss of heterozygosity. Our studies described an induction of tetraploidy/aneuploidy by a stable form of Aurora-B, leading to acquisition of transformation properties. It is intriguing to speculate that in some cancers, tetraploidy/aneuploidy induced by deregulated expression of a mitotic regulator represents a primary event that leads to unbalanced expression of a cluster of crucial genes and to cellular transformation.

Aneuploidy↗
PubMed2005

Prostate stem cells and prostate cancer.

Understanding prostate stem cells (PSCs) may provide insight for the design of therapeutics for prostate cancer. We have developed a quantitative in vivo colony-forming assay and have demonstrated that the Sca-1 antigen is present on the surface of a prostate cell subpopulation that possesses multiple stem cell properties. Immunofluorescent analysis demonstrates that Sca-1 is expressed by both basal and luminal cells in the proximal region of the adult prostate, but is not expressed by either lineage in more distal regions. The proximal region has been suggested as the PSC niche based on BrdU label-retention studies and the presence of distinct smooth-muscle cells that produce high levels of TGF-beta. Sca-1 is also expressed by nearly all cells within fetal prostate epithelial chords, suggesting Sca-1 may be conserved on PSCs throughout development. Malignant epithelial cells from TRAMP mice, as well as normal prostate cells with lentiviral-mediated alteration of the PTEN/AKT signaling pathway, give rise to PIN lesions and prostate cancer in vivo. Alteration of PTEN/AKT signaling in Sca-1-enriched PSCs also results in PIN lesions, suggesting that PSCs can serve as one target for prostate carcinogenesis.

Animals↗
PubMed2005

Wnt signalling in stem cells and cancer.

The canonical Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signalling has also been associated with cancer. This has raised the possibility that the tightly regulated self-renewal mediated by Wnt signalling in stem and progenitor cells is subverted in cancer cells to allow malignant proliferation. Insights gained from understanding how the Wnt pathway is integrally involved in both stem cell and cancer cell maintenance and growth in the intestinal, epidermal and haematopoietic systems may serve as a paradigm for understanding the dual nature of self-renewal signals.

Animals↗
PubMed2006

Future cancer management with stem cell knowledge and technology.

Cancer has been proposed as a result of abnormal control of growth and development of stem cells for more than century. This is the "cancer stem cell hypothesis". Both cancer and stem cells share many common especial properties. They are immortal and have good differentiation potential. In addition, organogenesis and carcinogenesis are very similar processes. Recently, more evidence and convincing data from stem cell biology research are supporting this concept. Furthermore, the research provides new promising approaches for cancer diagnosis and treatment based on stem cell knowledge and technology. Upcoming data and evidence may revolutionize cancer management, making it more effective and safer.

Forecasting↗
PubMed2006

Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.

Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying tumour radioresistance have remained elusive. Here we show that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction of tumour cells expressing CD133 (Prominin-1), a marker for both neural stem cells and brain cancer stem cells, is enriched after radiation in gliomas. In both cell culture and the brains of immunocompromised mice, CD133-expressing glioma cells survive ionizing radiation in increased proportions relative to most tumour cells, which lack CD133. CD133-expressing tumour cells isolated from both human glioma xenografts and primary patient glioblastoma specimens preferentially activate the DNA damage checkpoint in response to radiation, and repair radiation-induced DNA damage more effectively than CD133-negative tumour cells. In addition, the radioresistance of CD133-positive glioma stem cells can be reversed with a specific inhibitor of the Chk1 and Chk2 checkpoint kinases. Our results suggest that CD133-positive tumour cells represent the cellular population that confers glioma radioresistance and could be the source of tumour recurrence after radiation. Targeting DNA damage checkpoint response in cancer stem cells may overcome this radioresistance and provide a therapeutic model for malignant brain cancers.

AC133 Antigen↗
PubMed2004

Stem cell factor and macrophage-colony stimulating factor in patients with pancreatic cancer.

Stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) have assumed an increasing importance in cancer biology. In the present study we investigated the serum levels of these cytokines in pancreatic cancer patients in relation to controls and to patients with benign lesions of the pancreas (chronic pancreatitis group). The classical tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum levels of cytokines with tumor stage. We also defined the receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers. The cytokines were measured in 47 patients with pancreatic cancer, in 27 patients with chronic pancreatitis and in 35 healthy subjects. SCF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group, but only the serum levels of M-CSF, CEA and CA 19-9 were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of cytokines and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels correlated positively with the tested tumor markers. The M-CSF area under the ROC curve was higher than the SCF area. These results suggest that M-CSF is a better candidate for a pancreatic cancer tumor marker than SCF.

Adult↗
PubMed2005

Death-from-cancer signatures and stem cell contribution to metastatic cancer.

Genome-wide expression profiling studies reveal a transcriptionally distinct sub-type of human solid tumors with a marked propensity toward metastatic dissemination, highly malignant clinical behavior, and poor therapy outcome in cancer patients diagnosed with the early stage carcinomas of various origins. This sub-set of tumors acquires full metastatic potential, including an emergence and seeding of potent metastasis precursor cells, early in tumor progression. Collectively, these data suggest an early involvement in development of this transcriptionally defined sub-type of human carcinomas of a highly malignant combination of mutant alleles conferring the proclivity to metastasize and/or an engagement in transformation and tumor progression of stem cells and/or early progenitor cells. Enrichment of primary tumors with normal stem cells increases the likelihood of horizontal genomic transfer (large-scale transfer of DNA and chromatin) between stem cells and cancer cells via cell fusion and/or uptake of apoptotic bodies and generation of reprogrammed somatic cell hybrids with self-renewing highly malignant phenotype.

Alleles↗
PubMed2005

Hypothesis: cell plasticity, linking embryonal stem cells to adult stem cell reservoirs and metastatic cancer cells?

Embryonal stem (ES) cells are the earliest ontogenetically identifiable stem cells of the embryo proper for all subsequent mesenchymal stem cells and for highly specialized differentiated cells. This review characterizes, in a working hypothesis, the role of reversible EMT/MET (epithelialmesenchymal transition) as a manifestation of cell plasticity 1) in the development of ES cells to adult stem cells (hematopoietic stem cells) and 2) in metastasizing cancer cells. Animal studies support the concept that EMT/MET is a key manifestation of cell plasticity in the development of ES cells to adult stem cells, and in conversion of localized to metastasizing cancer cells. In fact, ES cells may persist to postnatal life, in cytologically verifiable form and/or within the frame of EMT/MET, as ultimate reservoir for adult stem cells. Furthermore, EMT could possibly serve as a conceptional link between physiologic and pathologic signaling pathways. Clonal confirmation in humans is necessary.

Adult↗
PubMed2003

[Hematopoietic stem cell transplant in cancer treatment].

Hematopoietic stem cell transplantation (HSCT) includes bone marrow, peripheral blood, cord blood, autologous, allogeneic, related or unrelated. These transplants have two main roles in cancer treatment, i.e., supportive treatment for marrow toxicity and immunotherapy for cancer cells. HSCT has also severe adverse reaction such as, bacterial fungal or viral infection by neutropenia, or graft versus host disease by the replacement of immune system. In autologous HSCT the main role is to prevent severe marrow toxicity which enables extreme high dose of anticancer drug administration. In allogeneic HSCT the main roles become both, support for marrow toxicity and immunotherapy, which possibly complicated with immunological adverse reactions. In mini-transplant or allogeneic transplant with reduced intensity, the main role is immunotherapy. These three kinds of transplants have each own indication and conducted in 17,472 patients till 2001 in Japan.

Hematopoietic Stem Cell Transplantation↗
PubMed2004

Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity.

Emerging evidence suggests cancer stem cells sustain neoplasms; however, little is understood of the normal cell initially targeted and the resultant cancer stem cells. We show here, by tracking individual human leukemia stem cells (LSCs) in nonobese diabetic-severe combined immunodeficiency mice serially transplanted with acute myeloid leukemia cells, that LSCs are not functionally homogeneous but, like the normal hematopoietic stem cell (HSC) compartment, comprise distinct hierarchically arranged LSC classes. Distinct LSC fates derived from heterogeneous self-renewal potential. Some LSCs emerged only in recipients of serial transplantation, indicating they divided rarely and underwent self-renewal rather than commitment after cell division within primary recipients. Heterogeneity in LSC self-renewal potential supports the hypothesis that they derive from normal HSCs. Furthermore, normal developmental processes are not completely abolished during leukemogenesis. The existence of multiple stem cell classes shows the need for LSC-targeted therapies.

Animals↗
PubMed2005

The paradox of response and survival in cancer therapeutics.

Although most patients with cancer respond to therapy, few are cured. Moreover, objective clinical responses to treatment often do not even translate into substantial improvements in overall survival. For example, patients with indolent lymphoma who achieved a complete remission with conventional-dose therapies in the prerituximab era did not experience a survival advantage over similar patients treated with a "watch and wait" approach. Several studies have also shown that neither the magnitude nor the kinetics of clinical response has an impact on survival in multiple myeloma. Recent data suggesting many malignancies arise from a rare population of cells that exclusively maintains the ability to self-renew and sustains the tumor (ie, "cancer stem cells") may help explain this paradox that response and survival are not always linked. Therapies that successfully eliminate the differentiated cancer cells characterizing the tumor may be ineffective against rare, biologically distinct cancer stem cells. New methods for assessing treatment efficacy must also be developed, as traditional response criteria measure tumor bulk and may not reflect changes in rare cancer stem cell populations. In this article, we discuss the evidence for cancer stem cells in hematologic malignancies and possible ways to begin targeting these cells and measuring clinical effectiveness of such treatment approaches.

Humans↗
PubMed2004

Self-renewal and solid tumor stem cells.

Solid tumors arise in organs that contain stem cell populations. The tumors in these tissues consist of heterogeneous populations of cancer cells that differ markedly in their ability to proliferate and form new tumors. In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. While the majority of the cancer cells have a limited ability to divide, a population of cancer stem cells that has the exclusive ability to extensively proliferate and form new tumors can be identified based on marker expression. Growing evidence suggests that pathways that regulate the self-renewal of normal stem cells are deregulated in cancer stem cells resulting in the continuous expansion of self-renewing cancer cells and tumor formation. This suggests that agents that target the defective self-renewal pathways in cancer cells might lead to improved outcomes in the treatment of these diseases.

Animals↗
PubMed2005

The role of adult stem cells in carcinogenesis.

The role of adult stem cells in tissue regeneration has attracted much interest because of its enormous therapeutic potential. Adult stem cells reside in every tissue of the body and have the ability to self-renew and to give rise to a high number of differentiated progeny. These are indeed the essential steps in tissue regeneration, which in some cases occurs constitutively, whereas in other cases happens in response to an injury. The identification of the key factors involved in self-renewal and differentiation pathways is at the top of the agenda of stem cell biologists. Interestingly, a number of factors that govern the fate of adult stem cells also play a role in malignant cell transformation, such as the Wnt cascade, Oct-4, Bmi-1 and Evi1. In addition, rare subpopulations of cancer stem cells were identified for leukemia and other solid tumors. These rare fractions of cancer stem cells are in large part responsible for maintaining the tumor mass, as they have the capacity to self-renew and to generate a high number of progeny via differentiation program. These findings can be considered a major breakthrough in cancer research. Currently, oncologists and stem cell biologists have two main goals: i) the assessment of the consistency of the line that divides adult stem cells and carcinogenesis; ii) to better characterize the biology of cancer stem cells. This new line of investigation may allow for the development of novel therapeutics and cancer diagnostics.

AC133 Antigen↗
PubMed2006

Lung cancer and lung stem cells: strange bedfellows?

Lung cancer is a significant disease with survival rates remaining poor despite numerous therapeutic advances during the last 30 years. Understanding lung cancer pathogenesis through murine modeling may improve future human therapies, and new data indicate that mutations within different endogenous stem cells situated throughout airways can drive cancer formation. Airway stem cells maintain prototumorigenic characteristics, including high proliferative capacity, multipotent differentiation, and a long lifespan relative to other cells. These cells localize to proximal airway submucosal glands/intercartilagenous rings, neuroepithelial bodies, and terminal bronchioles/bronchoalveolar duct junctions. Recent studies suggest that endogenous stem cell signaling and differentiation pathways are maintained within distinct cancer types, and that destabilization of this signaling machinery may initiate region-specific lung cancers. A better understanding of this relationship among stem cell regulation, cellular mutation, and lung cancer oncogenesis is critical for developing the next wave of lung cancer therapies.

Animals↗
PubMed2026

Emodin Induces AIF-Associated Apoptosis and Suppresses Wnt/β-Catenin Signaling in Colorectal Cancer Stem-Like Cells.

Colorectal cancer (CRC) remains a major cause of cancer-related mortality due to therapeutic resistance. Because colorectal cancer stem-like cells (CRCSCs) play a central role in tumor initiation and progression, therapeutic strategies addressing CSC-enriched populations are urgently needed. In this study, we investigated the anticancer effects of emodin, a natural anthraquinone, in CSC-enriched tumorsphere models. Emodin significantly suppressed the viability and self-renewal capacity of HCT116- and SW480-derived CSCs. It induced G0/G1 cell cycle arrest and markedly downregulated stemness-associated markers (CD44, CD133, ALDH1A1, SOX2, NANOG, and OCT4). Importantly, emodin-induced cell death was characterized by mitochondrial dysfunction, increased mitochondrial reactive oxygen species, loss of membrane potential, and nuclear translocation of apoptosis-inducing factor (AIF). This cytotoxicity was not rescued by the pan-caspase inhibitor Z-VAD-FMK, confirming caspase-independent apoptosis. Furthermore, network pharmacology and experimental validation identified GSK3β as a key target. Emodin reduced Wnt/β-catenin signaling by decreasing β-catenin stabilization and nuclear accumulation. Crucially, a rescue experiment utilizing LiCl confirmed that emodin's suppressive effects are mechanistically dependent on the GSK3β/Wnt/β-catenin axis. Collectively, emodin suppresses CRCSC characteristics in vitro by downregulating Wnt/β-catenin signaling and inducing AIF-associated caspase-independent apoptosis, highlighting its therapeutic potential against CRC.

Apoptosis-inducing factor (AIF)↗
PubMed2006

From embryonic stem cells to testicular germ cell cancer-- should we be concerned?

Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell for the vast majority of germ cell tumours -- it has been proposed that CIS cells could be derived from transformed primordial germ cells or gonocytes. Here, we review recent discoveries not only substantiating that initial hypothesis but also indicating that CIS cells have a striking phenotypic similarity to embryonic stem cells (ESC). Many cancers have been proposed to originate from tissue-specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS may be a very good example of a CSC, but with exceptional features due to the retention of embryonic pluripotency. In addition, considering the fact that pre-invasive CIS cells are transformed from early fetal cells, possibly due to environmentally induced alterations of the niche, we discuss potential risks linked to the uncontrolled therapeutic use of ESC.

Carcinoma in Situ↗
PubMed2005

Gastrointestinal stem cells and cancer: bridging the molecular gap.

Cancer is believed to be a disease involving stem cells. The digestive tract has a very high cancer prevalence partly owing to rapid epithelial cell turnover and exposure to dietary toxins. Work on the hereditary cancer syndromes including familial adenomatous polyposis (FAP) has led to significant advances, including the adenoma-carcinoma sequence. The initial mutation involved in this stepwise progression is in the "gatekeeper" tumor suppressor gene adenomatous polyposis coli (APC). In FAP somatic, second hits in this gene are nonrandom events, selected for by the position of the germ-line mutation. Extensive work in both the mouse and human has shown that crypts are clonal units and mutated stem cells may develop a selective advantage, eventually forming a clonal crypt population by a process called "niche succession." Aberrant crypt foci are then formed by the longitudinal division of crypts into two daughter units--crypt fission. The early growth of adenomas is contentious with two main theories, the "top-down" and "bottom-up" hypotheses, attempting to explain the spread of dysplastic tissue in the bowel. Initial X chromosome inactivation studies suggested that colorectal tumors were monoclonal; however, work on a rare XO/XY human patient with FAP and chimeric Min mice showed that 76% of adenomas were polyclonal. A reduction in tumor multiplicity in the chimeric mouse model has been achieved by the introduction of a homozygous tumor resistance allele. This model has been used to suggest that short-range interaction between adjacent initiated crypts, not random polyp collision, is responsible for tumor polyclonality.

Adenomatous Polyposis Coli↗
PubMed2006

Human neuroblastoma stem cells.

Human neuroblastoma is an embryonic cancer of the neural crest. Cellular heterogeneity is a characteristic feature of both tumors and derived cell lines. Recent studies have revealed that both cell lines and tumors contain cancer stem cells. In culture, these cells are self-renewing, multipotent, and highly malignant; in tumors their frequency correlates with a worse prognosis. Their identification and characterization should now permit a targeted approach to more effective treatment of this often fatal childhood cancer.

Humans↗