They examined cancer stem cell plasticity in which cancer stem cells can transition between non cancer stem cells noncsc and csc via in situ supporting a more stochastic model. Liver cancer is the second most common cause of cancerrelated death. By definition, csc exhibit selfrenewal activity and longterm cancerpropagating capacity 19. Jan 31, 2014 cancer stem cells covers a wide range of topics in cancer stem cell biology, including the functional characteristics of cancer stem cells and how theyre generated, where they are localized, the means by which cancer stem cells can be targeted, and how cancer stem cells can be reprogrammed back to normal tissue stem cells. Abstractalthough monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. Clonal evolution and csc models describe the basic mechanisms leading to tumour heterogeneity. Essentials of cancer stem cells and conceptual modeling. The aggressive nature of tnbc may be explained in part by the presence of breast cancer stem cells bcscs within tnbc tumors. Significant advances made recently in the cancer stem cell csc biology field have provided new. Cancer is a disease caused by the genetic alterations that lead to aberrant gene expression. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. Drug testing using in vitro models has been a major boost, not only in identifying potential therapeutic compounds, but also in increasing our understanding of their absorption, distribution, metabolism, and excretion adme properties. Lin lee institute of molecular and cellular biology. Cancer cells which have the capacity to colonize distant organs have the features of csc and, in addition, exert their tumorinitiating capacity under.
A new method for identifying stemlike cells in esophageal. Consistent with this idea, it was recently demonstrated in preclinical models that resistance to epigenetic therapies in aml emerges from a subpopulation of leukemia stem cells. Stem cells is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. The stem cell theory of cancer ludwig center stanford. Stem cells might be the target cells responsible for malignant transformation, and tumour formation may be a disorder of stem cell selfrenewal pathway. Mesenchymal and hematopoietic stem cells are described as well as mouse models that are employed to elucidate the properties and functionality of stem cells in cancer and the stem cell niche. This special issue of journal of clinical oncology is devoted to the emerging field of cancer stem cells cscs. Breast cancer research breast cancer stem cell markers the rocky road to clinical applications gabriela dontu corresponding author. Cscs population is responsible for tumour growth and progression figure 2b. Pdf with the cementing of the cancer stem cell csc concept, cancer biology and cancer drug discovery has attained a new avenue to approach cancer. Cancer stem cell niche models and contribution by mesenchymal. Clarke stanford institute for stem cell biology and regenerative medicine, stanford.
Toward understanding cancer stem cell heterogeneity in the. Improved experimental models are beginning to uncover a less rigid structure to csc biology, in which the concepts of functional plasticity and. The cancer stem cells concept is greatly changing the historic. Apart from their use in the immunoreconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The former population has been termed cancer stem cells cscs, tumorigenic cancer cells, or tumorinitiating cells, by various investigators, to indicate that only they can give rise to new tumors when transplanted into immunodeficient animals. Cancer stem cells, similarly housed adjacent to endothelial cells, proliferate and produce both other cancer stem cells and non cancer stem cell tumor cells. Here, we devise a theoretical framework to investigate how the tumor microenvironment tme modulates this spatial patterning. Department of public and allied health, bowling green state university, bowling green, oh 43403, usa. Jun 23, 2009 two currently popular hypotheses that attempt to explain intratumoral heterogeneity are the cancer stem cell and the clonal evolution models. Detection of cancer stem cells to detect cancer stem and precursor cells in multiple tissue types, use aldefluor. Each of these concepts has been investigated for some time, leading to the accumulation of findings that support one or the other. Rather, a tumor is a complex ecosystem containing tumor cells, as well as various infiltrating endothelial, hematopoietic, stromal, and other cell types that can influence the function of the tumor as a whole.
Jun 26, 2009 the investigation and study of cancer stem cells cscs have received enormous attention over the past 5 to 10 years but remain topics of considerable controversy. They examined cancer stem cell plasticity in which cancer stem cells can transition between noncancer stem cells noncsc and csc via in situ supporting a more stochastic model. The aberrant gene expression that results in loss of cell cycle control leads to the increased potential of cancer cell proliferation. Increasing data support cancer as a stem cellbased disease. Stem cells have been widely studied in the fields of cancer biology. These cells, which have been called tumorinitiating, cancer stem, or cancer stemlike cells, were found to possess characteristics of adult organ stem cells such as selfrenewal and multilineage differentiation, implicating a transformed normal stem cell as the cell of tumor origin. Role of stem cells in cancer therapy and cancer stem cells. It has been hypothesized that therapeutic failures often arise from adaptive responses in cancer stem cells. The discovery of the mechanism of acquisition of stem like properties by carcinoma cells via epithelialmesenchymal transition emt. This plasticity can occur independently of stemnessinducing factors and is indispensable for longterm metastatic growth. 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. Mar 17, 2020 liver cancer is the second most common cause of cancer related death. A novel model of liver cancer stem cells developed from.
Cancer stem cells cscs have the ability to selfrenew, invade, and metastasize, and are resistant to conventional chemotherapy and radiation therapy causing cancer recurrence after treatment 11. Since last two decades, the major cancer research has focused on understanding the characteristic properties and mechanism of formation of cancer stem cells cscs, due to their ability to initiate tumor growth, selfrenewal property and multidrug resistance. The volume covers extensive topics such as identification and isolation of cancer stem cells, animal models of cancer stem cells. The cancer stem cell theory is controversial because evidence for the existence of cancer stem cells relies solely on experiments that involve breaking down a tumour, taking out particular cells and then transplanting them. Mathematical models of cancer stem cells franziska michor from the computational biology center, memorial sloan kettering cancer center, new york, ny. The cancer stem cell csc concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are. This observation is traditionally explained by postulating variations in tumor microenvironment and coexistence of multiple genetic subclones, created by progressive and divergent accumulation of independent somatic mutations. Cancer stem cells cscs are a subpopulation of tumour cells that possess the stem cell properties of selfrenewal and differentiation. A new method for identifying stemlike cells in esophageal cancer cell lines. According to this second scenario, tumors act as caricatures of their corresponding normal tissues and are sustained in their growth by a pathological counterpart of normal adult stem cells, cancer stem cells. The principle concept of cancer stem cells csc has gained increasing acceptance in recent years 110.
Current concepts in bone metastasis, contemporary therapeutic. Breast cancer stem cell markers the rocky road to clinical. Department of biological sciences, bowling green state university, bowling green, oh 43403, usa 2. The leaky nature of blood vessels in a tumor allows for an abundance of inflammatory and bmderived progenitor cells within the mass of the tumor. The concept that cancer might arise from a rare cell.
The book also explores innovative therapeutic strategies in preclinical and clinical trials to target cancer stem. Resurgence of an old model for investigation of modern concepts of tailored therapy and cancer stem cells massimo moro, 1 giulia bertolini, 1 monica tortoreto, 2 ugo pastorino, 3 gabriella sozzi, 1 and luca roz 1. Models and concepts although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. In order to be able to eradicate these cscs with novel classes of anti cancer therapeutics, a better understanding of their biology and clinicallyrelevant traits is mandatory. Conversion of stem cells to cancer stem cells mdpi. Elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers.
This book encompasses a wide variety of human cancers that include but are not limited to leukemia, gliomas, breast, and prostate cancers. The cancer stem cell csc concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. Cancer stem cells, similarly housed adjacent to endothelial cells, proliferate and produce both other cancer stem cells and noncancer stem cell tumor cells. Cancer drug discovery programs involving cancer stem cells as a platform offer a discovery process with a high degree of therapeutic efficiency.
In this model, most cancer cells should possess several mutations that give the. Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. Some state that these cells are derived from normal stem cells that have acquired oncogenic mutations g, others refute this with the claim that cancer stem cells can arise from a committed progenitor cell that has acquired the properties of a stemcell during its cancerous transformation z1, while yet others suggest that these cells could. If the putative cancer stem cells are less sensitive to these therapies, then they will remain viable after therapy and reestablish the tumor. Indeed, recent advances have led to the identification of csc markers, csc targets, and the preclinical and clinical evaluation of the csceradicating curative potential of various drugs. Yet, many fundamental questions regarding the specific roles of stem cell in cancer progression and therapy remain elusive, impeding the effective clinical translation of stem cell research. Apr 16, 2019 since last two decades, the major cancer research has focused on understanding the characteristic properties and mechanism of formation of cancer stem cells cscs, due to their ability to initiate tumor growth, selfrenewal property and multidrug resistance. A new method for identifying stem like cells in esophageal cancer cell lines. Cancer stem cells wiley online books wiley online library. Patientderived xenografts of non small cell lung cancer.
In the presence of cell fusion factors, a normal stem cell may fuse with a transformed cell to form a mononucleated cell synkaryon or a. Opinions about the validity of the csc hypothesis, the biological properties of cscs, and the relevance of cscs to cancer therapy differ widely. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. By contrast, if therapies can be targeted against cancer stem cells. Cancer stem cells cscs have been found in different human cancers, and recent evidence indicates that breast cancer originates from. The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. Conversely, the cancer stem cell csc model postulates a hierarchical organization of cells such that only a small subset is responsible for sustaining tumorigenesis and establishing the cellular heterogeneity inherent in the primary tumor.
The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Two important related concepts of this hypothesis are that a tumors originate in either tissue stem cells or their immediate progeny through. Aug 11, 2017 elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. Sep 27, 2011 stem cells as in vitro models for drug discovery. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells. A highly effective tool for nonimmunological identification, the aldefluor fluorescent reagent system offers a novel approach to identify, evaluate and isolate stem and progenitor cells based on their expression of aldehyde. Stem cell concepts renew cancer research blood american. Jan 12, 2012 the cancer stem cell csc concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are. Jan 02, 2019 the presence of heterogeneous subsets of cancer stem cells cscs remains a clinical challenge. The cancer stem cell csc model has been established as a cellular mechanism that contributes to pheno. In this respect heterogeneity means presence of cells at different stages of maturation. The increasing complexity of the cancer stem cell paradigm. A tumor is not simply a bag of homogeneous malignant cells.
Mar 17, 2017 it has been hypothesized that therapeutic failures often arise from adaptive responses in cancer stem cells. The presence of heterogeneous subsets of cancer stem cells cscs remains a clinical challenge. It contains major revisions on cancer stem cells to include new culture models, additional interviews with leaders in progenitor cells, engineered eye tissue, and xeno organs from stem cells, as well as new information on organs on chips and adult progenitor cells. Dec 20, 2006 the former population has been termed cancer stem cells cscs, tumorigenic cancer cells, or tumorinitiating cells, by various investigators, to indicate that only they can give rise to new tumors when transplanted into immunodeficient animals. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture the known attributes of cancer stem cells and their potential contribution to treatment response, and metastases. Glioblastoma, the most malignant type of primary brain tumor, is one of the solid cancers where cancer stem cells have been isolated, and studies have suggested resistance of those cells to chemotherapy and radiotherapy. Cancer stem cells theories and practice intechopen. Cancer cells, stem cells and cancer stem cells have for a long time played a significant role in the biomedical sciences. The discovery of the mechanism of acquisition of stemlike properties by carcinoma cells via epithelialmesenchymal transition emt. Though cancer therapy is more effective than it was a few years ago, the truth is that still none of the current nonsurgical treatments can cure cancer effectively. Cancer cells which have the capacity to colonize distant organs have the features of csc and, in addition, exert their tumorinitiating capacity under adverse microenvironmental conditions.
We find that a spatial gradient of emtinducing signal. Pdf stem cells in human breast cancer researchgate. Gabriela dontu 0 0 0 department of internal medicine, university of michigan, ann arbor, michigan 48109, usa lately, understanding the role of cancer stem cells in tumor initiation and progression became a major focus in stem cell biology and in cancer research. The cancer stem cell model assumes that tumour tissue is hierarchically organized.
Every type of tumours including liver cancer contains cancer stem cells cscs. Cancer stem cells the current status of an old concept. Pdf chapter 10cancer stem cell models and role in drug. Cancer stem cells in basic science and in translational. These subsets often occupy different regions in the primary tumor and have varied epithelialmesenchymal phenotypes. Cancer stem cells csc which possess selfrenewal properties and genomic instability are considered to be an engine of tumor evolution. The initiation and progression of malignant tumors is driven by distinct subsets of tumorinitiating or cancer stem like cells cscs which develop therapyapoptosis resistance and selfrenewal capacity. Cancer stem cells theories and practice is firmly grounded in the latest results on cancer stem cells cscs from worldclass cancer research laboratories, but its twentytwo chapters also tease apart cancers vulnerabilities and identify opportunities for early detection, targeted therapy, and reducing remission and resistance. The mechanistic basis of tumor heterogeneity has been uncertain. Methods and protocols, preeminent researchers have compiled cancer stem cell research techniques and protocols to promote healthy competition, discourse, and collaboration in this vital field. Department of medical science, national tsinghua university the cancer stem cell csc hypothesis yi. Plasticity of lgr5negative cancer cells drives metastasis. Plasticity of lgr5negative cancer cells drives metastasis in.
In each of these cases, a minority subpopulation of cancer cells with phenotypic and functional features of neural stem cells appears uniquely capable of proliferating in culture and forming tumors in vivo. The goal of this article is to introduce general concepts of csc biology to clinicians, and to provide a framework for their understanding the cscbased approach to the development of novel diagnostics, therapeutics, and prevention strategies in oncology. The leaky nature of blood vessels in a tumor allows for an abundance of inflammatory and bm. Since their description and identification in leukemias and solid tumors, cancer stem cells csc have been the subject of intensive research in translational oncology. The cancer stem cell model also applies to some cancers of the nervous system, such as medulloblastoma, gliomas, and ependymomas 11,12,56. Targeting the roots of cancer, seeds of metastasis, and sources of therapy resistance introduces the basic concepts and advanced understanding of cancer stem cells, covering general overviews, organspecific identifications, and their characteristic mechanisms. Although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. Here, we report the establishment of cscenriched cultures derived from human glioblastoma specimens. They demonstrate that the majority of metastases are seeded by lgr5. Clinical and therapeutic implications of cancer stem cells. For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. This model, first developed in human myeloid leukemias, is today being extended to solid tumors, such as breast and brain cancer.
Concepts, challenges, and therapeutic opportunities. In the following commentary, we discuss the nature of the debate, the parameters by. They demonstrate a model that includes aspects of both the stochastic and csc models. Evolution of the cancer stem cell model cell press. Cancer stem cells covers a wide range of topics in cancer stem cell biology, including the functional characteristics of cancer stem cells and how theyre generated, where they are localized, the means by which cancer stem cells can be targeted, and how cancer stem cells can be reprogrammed back to normal tissue stem cells.
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