Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cancer stem cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2006

The cancer stem cell hypothesis: a work in progress.

There is a growing body of evidence that supports the idea that malignant tumors are initiated and maintained by a population of tumor cells that share similar biologic properties to normal adult stem cells. This model, the cancer stem cell (CSC) hypothesis, is based on the observation that tumors, like adult tissues, arise from cells that exhibit the ability to self-renew as well as give rise to differentiated tissue cells. Although the concept of the CSC is not entirely new, advances made over the past two decades in our understanding of normal stem cell biology in conjunction with the recent application of these concepts to experimentally define CSCs have resulted in the identification of CSCs in several human malignancies.

Adult Stem Cells↗
PubMed2006

Cancer stem cells: an old idea--a paradigm shift.

Although the concept that cancers arise from "stem cells" or "germ cells" was first proposed about 150 years ago, it is only recently that advances in stem cell biology have given new impetus to the "cancer stem cell hypothesis." Two important related concepts of this hypothesis are that (a) tumors originate in either tissue stem cells or their immediate progeny through dysregulation of the normally tightly regulated process of self-renewal. As a result of this, (b) tumors contain a cellular subcomponent that retains key stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation albeit aberrant that contributes to cellular heterogeneity. Recent experimental evidence in a variety of tumors has lent strong support to the cancer stem cell hypothesis that represents a paradigm shift in our understanding of carcinogenesis and tumor cell biology. This hypothesis has fundamental implications for cancer risk assessment, early detection, prognostication, and prevention. Furthermore, the current development of cancer therapeutics based on tumor regression may have produced agents that kill differentiated tumor cells while sparing the rare cancer stem cell population. The development of more effective cancer therapies may thus require targeting this important cell population.

Animals↗
PubMed2006

Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.

Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy.

Apoptosis↗
PubMed2026

Engineering CRISPR nanoplatforms to deplete cancer stem cells: Delivery checkpoints, target plasticity, and clinical viability.

Cancer stem cells (CSCs) sustain tumor initiation, therapy resistance, and relapse, yet evade durable control because they switch phenotype, enter quiescence, shelter within protective niches, resist drug efflux, and share markers with normal stem cells. Programmable CRISPR editing can disable intracellular self-renewal dependencies that antibodies and small molecules cannot reach, whereas only nanoscale carriers can confine such editing to intended cells; neither component alone solves the CSC problem. This review reframes CSC-directed CRISPR nanomedicine as an integrated design problem. We examine why target plasticity defeats static single-marker targeting; the sequential delivery checkpoints spanning blood stability, organ selection, tumor penetration, CSC recognition, endosomal escape, and productive editing; and advanced architectures including organ-selective lipid nanoparticles, biomimetic and vesicle carriers, metal-organic frameworks, and logic-gated systems. Genotoxicity, immunogenicity, incomplete depletion, manufacturing reproducibility, and absent CSC-specific clinical evidence remain limiting. Clinical viability, not imminent cure, is the realistic near-term objective.

Neoplastic Stem Cells↗
PubMedDate not supplied

Scale-up of breast cancer stem cell aggregate cultures to suspension bioreactors.

It has been hypothesized that breast tumor formation results from the activity of a scarce population of cells known as Breast Cancer Stem Cells (BrCSCs) and that the development of effective breast cancer therapies may therefore ultimately rely upon the ability to effectively target these cells for eradication. The scarcity of BrCSCs in vivo severely compromises research on these populations, as analyses are restricted to those requiring small cell numbers, and has become a major impediment to the development of therapeutic strategies against breast cancer. Through the culture of murine tissue aggregates containing a population of BrCSCs, this study demonstrates the ability of propagating this scarce population in a controlled and reproducible manner, within suspension bioreactors. A rigorous theoretical framework has been developed in order to understand and characterize the implications of oxygen mass transfer within aggregates upon scale-up and thereby provide a foundation for the scale-up of aggregate cultures. A two-factor, two-level factorial experimental design was also performed in order to assess the effects of inoculation density and hydrodynamic shear upon cell yield. We discovered that the culture of the murine aggregates in a relatively low shear environment (tau(max) = 0.20 Pa) and inoculated at 3.50 x 10(4) cells/mL resulted in the best yields for the range of conditions investigated in suspension bioreactors. A detailed study on the oxygen uptake kinetics of the aggregates also revealed that the uptake rates were not significantly affected by mass transfer limitations, as uptake rates of aggregate cultures were found to be comparable to those observed in single cell cultures. Cells propagated in a process controlled 500 mL suspension bioreactor resulted in growth kinetics that were comparable to those observed in 125 mL bioreactors. Doubling times in the 500 mL vessel were found to be 23.9 h and attained a maximum cell density of 1.20 x 10(6) cells/mL. After enumerating the number of BrCSCs, this resulted in an approximately 20-fold increase in BrCSC numbers in batch suspension cultures. With greater attention being applied to BrCSCs, their propagation in suspension bioreactors makes available experimental avenues that are not currently accessible and may thereby enable the development of more effective therapeutic drugs for the treatment of breast cancer.

Animals↗
PubMed2006

Leukemia stem cells.

Cancer is a multifaceted disease in which cell proliferation is no longer under normal growth control. Accumulating data have suggested the existence of cancer stem cells, a minor population of tumor cells that possess the stem cell property of self-renewal and that are responsible for the initiation and maintenance of cancer. The knowledge of cancer stem cell biology is most advanced in research on the hematopoietic cancer, leukemia. With the identification of leukemia stem cells (LSCs) capable of repopulating nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, this body of research has led to conclusive proof for cancer stem cells. This review focuses on the biological characterization of LSCs for each type of leukemia, which has provided key insights into leukemogenic pathology and LSC-targeted therapies.

Animals↗
PubMed2006

[Cancer initiating cell theory: popularity and controversies].

The cancer stem cell model proposes that most tumors are derived from a single cell that is transformed into a cancer-initiating cell (cancer stem cell). Cancer stem cells have the capacity to proliferate, differentiate, and form tumors in vivo. However, the origin of cancer stem cells remains controversial. Normal stem cells are regarded as an ideal candidate for the origin of cancer stem cells when take similar characters and signaling pathways between them into consideration. In addition,cell fusion is an important physiologic process during development and tissue repair,and is closely related to several fundamental features of tumors,and thus could be involved in the development of cancer stem cells.

Animals↗
PubMed2006

The cancer stem cell: evidence for its origin as an injured autoreactive T cell.

This review explores similarities between lymphocytes and cancer cells, and proposes a new model for the genesis of human cancer. We suggest that the development of cancer requires infection(s) during which antigenic determinants from pathogens mimicking self-antigens are co-presented to the immune system, leading to breaking T cell tolerance. Some level of autoimmunity is normal and necessary for effective pathogen eradication. However, autoreactive T cells must be eliminated by apoptosis when the immune response is terminated. Apoptosis can be deficient in the event of a weakened immune system, the causes of which are multifactorial. Some autoreactive T cells suffer genomic damage in this process, but manage to survive. The resulting cancer stem cell still retains some functions of an inflammatory T cell, so it seeks out sites of inflammation inside the body. Due to its defective constitutive production of inflammatory cytokines and other growth factors, a stroma is built at the site of inflammation similar to the temporary stroma built during wound healing. The cancer cells grow inside this stroma, forming a tumor that provides their vascular supply and protects them from cellular immune response. As cancer stem cells have plasticity comparable to normal stem cells, interactions with surrounding normal tissues cause them to give rise to all the various types of cancers, resembling differentiated tissue types. Metastases form at an advanced stage of the disease, with the proliferation of sites of inflammation inside the body following a similar mechanism. Immunosuppressive cancer therapies inadvertently re-invigorate pathogenic microorganisms and parasitic infections common to cancer, leading to a vicious circle of infection, autoimmunity and malignancy that ultimately dooms cancer patients. Based on this new understanding, we recommend a systemic approach to the development of cancer therapies that supports rather than antagonizes the immune system.

Animals↗
PubMed2006

Identifying cancer stem cells in solid tumors: case not proven.

Building on studies of leukemia, a number of recent articles have reported data suggesting that cancer stem cells could be isolated from solid human cancers. Some of these reports have speculated that the isolation of these cells will allow the identification of the specific molecular properties that can be targeted for therapeutic purposes. Although previous work with animal model systems also suggests the presence of stem cells in solid tumors, there remain many uncertainties, both theoretical and technical, about the interpretation of the current results. The case that a small proportion of cells in solid tumors are specific cancer stem cells and that these cells can be successfully identified and isolated has not yet been proven.

Animals↗
PubMed2006

Successful therapy must eradicate cancer stem cells.

Despite significant improvements in cancer therapy, tumor recurrence is frequent and can be due to a variety of mechanisms, including the evolution of resistance and tumor progression. Cancer stem cells have been postulated to maintain tumor growth similar to normal stem cells maintaining tissue homeostasis. Recently, the existence of these malignant stem cells has been proven for hematological as well as some solid tumors. Tumor stem cells are not targeted by standard therapy and might be responsible for treatment failure and tumor recurrence in many patients. We designed a simple mathematical model to demonstrate the importance of eliminating tumor stem cells. We explored different therapeutic scenarios to illustrate the properties required from novel therapeutic agents for successful tumor treatment. We show that successful therapy must eradicate tumor stem cells.

Animals↗
PubMed2007

Donor cell leukemia: insight into cancer stem cells and the stem cell niche.

Donor cell leukemia (DCL) is a rare complication of hematopoietic cell transplantation (HCT). Its incidence has been reported between 0.12% and 5%, although the majority of cases are anecdotal. The mechanisms of leukemogenesis in DCL may be distinct from other types of leukemia. Possible causes of DCL include oncogenic alteration or premature aging of transplanted donor cells in an immunosuppressed person. Although many studies have recently better characterized leukemic stem cells, it is important to also consider that both intrinsic cell factors and external signals from the hematopoietic microenvironment govern the developmental fate of hematopoietic stem cells (HSCs). Therefore, in cases of DCL, alteration of the microenvironment after HCT may increase the likelihood that some progeny of normal HSCs become leukemic. This complex intercommunication between cells, growth factors, and cytokines in the hematopoietic microenvironment are critical to balance HSC self-renewal, proliferation, and differentiation. However, this homeostasis is likely perturbed in the development of DCL, allowing unique insight into the stimuli that regulate normal and potentially abnormal hematopoietic development. In this article, we discuss the possible pathogenesis of DCL, its association with stem cells, and its likely dependence on a less-supportive stem cell niche.

Cell Differentiation↗
PubMed2007

Cancer stem cells and oncology therapeutics.

PURPOSE OF REVIEW: An overview of the latest developments in the cancer stem cells field and their potential use in the oncology drug discovery process. RECENT FINDINGS: Recent studies provided evidence of the existence of a subpopulation of cells within a variety of tumor types with a tumorigenic potential that is lacking in the rest of the cells within these tumors. There is mounting evidence that such cells exist in almost all tumor types. Work on the characterization of these cells suggests that deregulation of pathways responsible for stem cell self-renewal is a likely requirement for carcinogenesis and targeting such pathways might be curative. Progress has been made to develop more relevant in-vitro and in-vivo models that incorporate these findings. SUMMARY: Cancer stem cells have been identified in a variety of tumors. Characterization of these cells, determining how they originate and developing relevant assays is a work in progress. Incorporating these findings in the cancer drug discovery process might lead to better therapeutics.

Animals↗
PubMed2026

Targeting cancer stem cells predicts response and reverses chemoresistance in ascites-derived ovarian cancer organoids.

BACKGROUND: Ovarian cancer (OC) is frequently diagnosed at an advanced stage, where tumor heterogeneity and rapid development of chemoresistance contribute to a poor prognosis. The lack of reliable predictive biomarkers further hinders the development of effective treatment strategies. Patient-derived organoids (PDOs) have recently emerged as promising preclinical models with the potential to predict therapeutic responses. METHODS: OC PDOs were generated from ascites samples representing diverse histological subtypes. Histological and genomic fidelity to parental tumors was confirmed through histopathological analysis and whole-exome sequencing. Drug sensitivity to cisplatin and poly (ADP-ribose) polymerase (PARP) inhibitors was evaluated and correlated with 1-year clinical outcomes. We also investigated the therapeutic efficacy of oncolytic herpes simplex virus 2 (OH2) both as a single agent and in combination with cisplatin. The expression of cancer stem cell (CSC) markers CD44 and ALDH1A1 under treatment conditions was analyzed using immunohistochemistry and flow cytometry. RESULTS: PDOs were successfully established with an 86.2% success rate. These PDOs faithfully recapitulated the histopathological and genomic features of their corresponding tumors, maintaining intratumoral heterogeneity, and were amenable to xenotransplantation. Drug sensitivity assays demonstrated that PDOs accurately predicted patient-specific responses to cisplatin and PARP inhibitors. OH2 exhibited direct cytotoxicity in both cisplatin-sensitive and cisplatin-resistant PDOs, reducing cell viability by 20-60%. Notably, the combination treatment with OH2 and cisplatin enhanced antitumor efficacy, resulting in a significant reduction of the CD44+CSC subpopulation. CONCLUSIONS: Ascites-derived OC PDOs represent a robust platform for individualized drug testing. The combination of OH2 and cisplatin offers a novel and effective strategy for circumventing chemoresistance in OC.

Female↗
PubMed2006

Strategies to eliminate cancer stem cells: clinical implications.

Over the past two decades, major advances in our understanding of cancer have translated into only modest increments in survival for the majority of cancer patients. Recent data suggesting cancers arise from rare self-renewing stem cells that are biologically distinct from their more numerous differentiated progeny may explain this paradox. Current anticancer therapies have been developed to decrease the bulk of the tumour mass (i.e. the differentiated cancer cells). Although treatments directed against the bulk of the cancer may produce dramatic responses, they are unlikely to result in long-term remissions if the rare cancer stem cells are also not targeted. Conversely, treatments that selectively attack cancer stem cells will not immediately eliminate the differentiated cancer cells, and might therefore be prematurely abandoned if clinical activity is judged solely by traditional response criteria that reflect changes in the bulk of the tumour. Re-examining both our pre-clinical and clinical drug development paradigms to include the cancer stem cell concept has the potential to revolutionize the treatment of many cancers.

Antineoplastic Agents↗
PubMed2005

Cancer stem cells: lessons from leukemia.

A fundamental problem in cancer research is identification of the cell type capable of initiating and sustaining growth of the tumor--the cancer stem cell (CSC). While the existence of CSCs was first proposed over 40 years ago, only in the past decade have these cells been identified and characterized in hematological malignancies. Recent studies have now described CSCs in solid tumors of the breast and brain, raising the possibility that such cells are at the apex of all neoplastic systems. An appreciation of the biological distinctness of CSCs is crucial not only for the design of studies to understand how tumorigenic pathways operate but also for the development of specific therapies that effectively target these cells in patients.

Animals↗
PubMed2005

Telomerase and cancer stem cells.

Telomerase is critical for the integrity of stem cell compartments. Mutations in telomerase components lead to telomere shortening and hematopoietic stem cell failure in autosomal dominant dyskeratosis congenita and aplastic anemia. Telomerase activity is readily detected in most cancers but not in adult somatic cells. The telomere hypothesis for cancer states that telomerase is reactivated in late stages of carcinogenesis. However, recent evidence has suggested a stem cell origin for certain cancers, implying that the genetic alterations that lead to cancer accumulate in tissue-specific stem cells and not in adult somatic cells. In these cancers, stem cells would already have telomerase and it would not need to be reactivated. Here, we reconsider the telomere hypothesis in view of this evidence and propose that, rather than telomerase reactivation, enzyme activity may increase in later stages of carcinogenesis due to increased expression or efficient assembly of telomerase components. Understanding these mechanisms will refine approaches to telomerase inhibition in cancer.

Dyskeratosis Congenita↗
PubMed2025

Connexin 43 drives glioblastoma cancer stem cell phenotypes through a WNK lysine-deficient protein kinase 1-c-MYC signaling axis.

The coordination of cellular processes such as growth and survival relies on communication between cells through gap junctions. Connexin proteins comprise gap junctions and also function to mediate protein-protein interactions and communication with the extracellular space via hemichannels. Despite their essential roles, connexin function in cancer is context dependent, with connexin 43 (Cx43) reported to both promote and suppress tumor growth in glioblastoma, the most common primary malignant brain tumor. Here, we detect primarily intracellular expression of Cx43 in glioblastoma patient-derived cancer stem cells and demonstrate that Cx43 is essential for their survival, self-renewal, and tumor initiation. Mechanistically, Cx43 depletion reduces c-MYC expression through reduced levels of the upstream mediator WNK lysine-deficient protein kinase 1 (WNK1). WNK1 depletion phenocopies Cx43 knockdown and reduces c-MYC expression and tumor initiation. Together, these results define a signaling axis downstream of Cx43 that promotes tumor growth and cancer stem cell phenotypes in glioblastoma.

Connexin 43↗