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. It has also been suggested that cancer stem cells are more resistant to chemo and radiotherapy than other cells in a tumour. Although stem celllike cancer cells or cancer stem cells csc were experimentally demonstrated as early as 1952, it was not until relatively recently that advances in normal stem cell research have allowed application of many stem cell methodologies to studying csc, leading to the revival and explosion of csc research in the past decade. Cancer research in the second half of the last century was dominated by the clonal evolution model, a concept whereby each cell within a tumour has equal potential in acquiring stepwise, genetic andor epigenetic changes, conferring growth advantages and generating new tumours fig. Tumour cells are heterogeneous in terms of morphology, metabolism, proliferation rate, ability to metastasise and other features. 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. The evolving concept of liver cancer stem cells article pdf available in molecular cancer 164 january 2017 with 106 reads how we measure reads. Cancer stem cells cscs seek out a niche created within the tumor 3d microenvironment 5.
These cells have been called cancer stem cells csc, tumor initiating cells tic and stemloids. Genetic analyses have shaped much of our understanding of cancer. The major malignant phenotypes of cancer, including recurrence, metastasis, and chemoresistance, are related to the presence of cancer stem cells cscs. The term itself was coined in a highly cited paper in 2001 by biologists tannishtha reya, sean j. This article puts forward the current theory that there are cancer stem cells in much the same way as there are other stem cells. Elucidating the origin of and dynamic interrelationship between intratumoral cell subpopulations has clear clinical significance in helping to understand the cellular basis of treatment response, therapeutic resistance, and tumor relapse. Concept of cellular heterogeneity is displayed in both normal and cancer systems, with the presence of distinct cellular subpopulation. Recent observations, however, have highlighted many complexities and challenges. The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. A tumor is not simply a bag of homogeneous malignant cells.
The evolving landscape of cancer stem cells and ways to. Cancer stem cells the current status of an old concept. Ernest mcculloch and colleagues in the 1960s that provided first definitive evidence of adult stem cells 2, 3, 4. Cancer stem cells cscs are cancer cells found within tumors or hematological cancers that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. The stem cell theory of cancer ludwig center stanford. During the past decade, a stemcelllike subset of cancer cells has been identified in many malignancies. The cancer stem cell csc concept, which arose more than a decade ago, proposed that tumor growth is sustained by a subpopulation of highly malignant cancerous cells. The major malignant phenotypes of cancer, including recurrence, metastasis, and chemoresistance, are related to t. From the mid19th century when the first theory on the embryonic origin of cancer was formulated to works on embryonal carcinoma cells in the mid20th century, many steps have been crossed leading to the current cancer stem cell theory postulating that tumor growth is supported by a small fraction of the.
The evolving concept of liver cancer stem cells molecular. Cancer stem cells, a fuzzy evolving concept scienceopen. The concept of cancer stem cells emerges from the discovery of tumor heterogeneity. Heiko enderling central to the debate about cancer stem cells in solid tumors is the proportion of cells that can initiate. The cancer stem cell concept of tumor development, which has been experimentally proven by john dick and coworkers more than 20 years ago, suggests that cancer cells differ in their tumor initiating properties and population of tumor cells called cancer stem cells csc resides on top of the tumor cell hierarchy and maintains tumor.
An evolving concept the cancer stem cell csc concept derives from the fact that cancers are dysregulated tissue clones. The evolving concepts of cancer stem cells in head. Figure 7 compares the traditional and evolving conceptual views of stem cells. The clonal evolution ce model and the cancer stem cell csc model. The evolving concept of liver cancer stem cells liver cancer is an often fatal malignant tumor with a high recurrence rate and chemoresistance. Cancer stem cells modulate patterns and processes of evolution in. Cancer stem cells were first identified by john dick in acute myeloid leukemia in the late 1990s. Models of the cancer stem cell concept to explain tumor heterogeneity.
The model predicts at least two distinct subpopulations. Other teams subsequently reported finding apparent cancer stem cells in solid tumors such as breast, colon, brain, and pancreas. The evolving concept of cancer and metastasis stem cells. 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. The evolving concepts of cancer stem cells in head and neck. Cancer stem cells cscs may occur at any stage of cancer and are implicated in the occurrence of resistance, recurrence, and metastasis. Recent findings cscs have been prospectively isolated from bladder cancer tissues from patient specimens, established cancer cell lines and xenografts, based on the expression of a combination of cell surface receptors, cytokeratin markers, drug transporters and the efficient efflux of the hoechst 33 342 dye side population. If a cancer treatment destroys the bulk of a tumour but leaves behind cancer stem cells, then those cancer stem cells can continue to selfrenew and can cause the tumour to regrow. They differ in their morphology, genetics, cell surface markers, proliferation kinetics, tumorigenicity, and response to therapy 4. The superb demonstration of the role of stem cells in embryogenesis, and in the renewal of adult tissues such as blood, has quite naturally led to the concept that a similar model may apply to cancer. Recent improvements in immunotherapy targeting of tumourassociated. Dec 10, 2014 as regards their morphology and biology, tumours consist of heterogeneous cell populations.
Evolution of the cancer stem cell model cell press. Wed like to understand how you use our websites in order to improve them. The cancer stem cell concept the concept of cancer stem cells csc arose from the discovery that a majority of cells from some human leukemia acute myeloid leukemia, at different stages of differentiation, originated from transformed undifferentiated pluripotent stem cell. Cancer stem cells csc, together with clonal evolution driven by genetic alterations, generate cancer cell heterogeneity commonly observed in. The book also explores innovative therapeutic strategies in. By definition, both cscs and normal tissue stem cells possess selfrenewal capacity. Through their adaptation of an in vivo spleen colony formation assay, where donor bone marrow cells bmcs were transplanted into a pre. Recent improvements in immunotherapy targeting of tumour. The cancer stem cell csc concept, which arose more than a decade ago, proposed that tumor growth is sustained by a subpopulation of. The clinical impact of cancer stem cells lathia 2020. The latter is believed to be mainly due to the existence of a subpopulation of highly plastic stem like cells within the tumor, known as cancer stem cells cscs, which have been shown to have unique metabolic, autophagic, invasive, and chemoresistance properties that allow them to continuously selfrenew and escape chemotherapeutic elimination.
The everevolving concept of the cancer stem cell in. Nov 22, 20 the cancer stem cells csc hypothesis represents a pathological extrapolation of the physiological concept of embryonic and somatic stem cells. The article could make a good basis for a general discussion of the topic of cancer, including cancer research and treatments, diagnosis and survival rates. Targeting cancer stem cells may be a more effective way to overcome cancer resistance and prevent the spread of squamous cell carcinoma. These cells, referred to as cancer stem cells cscs, are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population that drives growth and progression. Through the revolutionary concept of cancer stem cells, cancer research has been reinvigorated to study the role of these unique cells in cancer propagation and as targets of innovative therapies. Method to convert stem cells into cancer stem cells mdpi. The key factor that phenotypically differentiates cscs from embryonic or adult stem cells is their unregulated, and primarily symmetric, cell division 8, 9.
Analysis of recent data suggests that adult stem cells can generate different. The cancer stem cell csc hypothesis suggests that tumors are sustained exclusively by a small population of the cells with stem cell properties. Cancer stem cells are a progressive concept to account for the cell biological nature of cancer. An evolving concept the cancer stem cell csc concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in. The latter is believed to be mainly due to the existence of a subpopulation of highly plastic stemlike cells within the tumor, known as cancer stem cells cscs, which have been shown to have unique metabolic, autophagic, invasive, and chemoresistance. Intratumoral heterogeneity ith at the cellular, genetic, and functional levels has been shown to occur to a startling degree in many cancers, and is increasingly appreciated as a key determinant of treatment failure and disease recurrence. The cancer stem cell model emerged in the mid1990s, when stem cell biologist john dick of the university of toronto reported that his team had isolated rare cells in the blood of people with leukemia that seemed to play a key role in the cancer. Cscs are therefore tumorigenic tumorforming, perhaps in contrast to other nontumorigenic cancer cells. We believe that the operational term tumorpropagating cells tpc are more suitable see appendix for terminology 4, 5. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Pdf the evolving concept of liver cancer stem cells. The ever evolving concept of the cancer stem cell in pancreatic cancer sandra v alle 1,2,3, id, laura martinhijano 1,2,3, id, sonia alcal a 1,2,3.
These cells, termed cscs, comprise the top of the tumor cell hierarchy and have been isolated from many leukemias and. Heiko enderling central to the debate about cancer stem cells in solid tumors is the proportion of cells that can initiate, propagate, and reinitiate tumors. Although such patients blood teems with aberrant white blood cells, only a few of them were capable of growing into a new leukemia when injected. Abstract the cancer stem cell csc concept has important therapeutic implications. It is noteworthy that this year marks the 20 th anniversary of the first experimental proof of cscs existence. Despite the controversies regarding the cancer stem cell model, it has the potential to provide a foundation for new innovative treatment targeting the roots of cancer. Since the early 2000s they have been an intense cancer research focus. Adult stem cells for tissue repair a new therapeutic.
A miniscule number of cells within an in vitro 3d tumor spheroid or an in vivo tumor exhibit stem celllike characteristics including 1 slowed proliferation rate 2 selfrenewal capabilities and 3 undifferentiated phenotype that can undergo multilineage differentiation. Tumor heterogeneity refers to the existence of different cellular types bearing different properties within the tumor. The everevolving concept of the cancer stem cell in pancreatic cancer. Within a malignant tumor or among the circulating cancerous cells of a leukemia, there can be a variety of types of cells. The relationships between cancer and stemness have a long history that is traced here.
An initially assumed minor subpopulation is confronted with recent. The concept of cancer stem cells in some tissues was challenged in its entirety by sean morrison, a coauthor of the article that first identified breast cancer stem cells, 18 who in 2008 showed that as many as 27% of unselected melanoma cells from different patients form tumors under permissive conditions. Pdf the everevolving concept of the cancer stem cell in. In its initial definition, it encompassed the hypothesis of a qualitatively distinct population of immortal cancer cells originating from somatic stem cells, which generate in xenotransplants by a deterministic irreversible process, the hierarchy of.
Adult human stem cells that are intrinsic to various tissues have been described and characterized, some only recently. Adult stem cells for tissue repair a new therapeutic concept. Pdf cancer stem cells cscs have the ability to selfrenew and are present in most. The concept of cancer stem cells cscs has attracted researchers attention since the beginning of the 21 st century. The cancer stem cells csc hypothesis represents a pathological extrapolation of the physiological concept of embryonic and somatic stem cells. Like normal stem cells, the cancer stem cells carried distinctive surface proteins and were selfrenewing. As a result, the cancer stem cell concept cannot be universally applicable, based on complex evolution, phenotypic heterogeneity and therapeutic challenges of many human cancers, making difficult. Pancreatic cancer stem cells cscs have been first described in 2007 and since then have emerged as an intriguing entity of cancer cells with distinct functional features including self. Cscs have been identified in most tumors and are responsible for the initiation, recurrence, and resistance of different cancers. The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The only cells being able to selfrenew and produce a heterogeneous tumour cell population are cancer stem cells.
Liver cancer is an often fatal malignant tumor with a high recurrence rate and chemoresistance. However, as initially alluded to in the 19th century and pioneered by the discovery of many types of. The cancer stemlike cell csc hypothesis postulates that a small population of cells in a cancer has selfrenewal and clonal tumor initiation. The evolving concepts of cancer stem cells in head and. 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. Therefore, cscs may be the roots and ideal target for therapeutic intervention. Although the term stem cell received its current definition in the late 1800s it was not until the seminal work by dr. Although the csc concept will have clinical relevance in specific cases, accumulating evidence suggests that it will be imperative to target all csc subsets within. Cancer stem cells cscs with therapeutic resistance and plasticity can be found in various types of tumors and are recognized as attractive targets for treatments. In vitro csc models will be of great help in revisiting the mechanism of cancer development, as well as the tumor. One of the first evidences that tumors are heterogeneous emerged from the works of rudolf virchow.
In the past few decades, cscs have been identified and characterized in many tumors including liver cancer. The evolving concept of cancer stemlike cells in thyroid cancer and. The evolving concept of liver cancer stem cells molecular cancer. However, it is becoming increasingly clear that cancer cells display features of normal tissue organization, where cancer stem cells cscs can drive tumor growth. Pdf the evolving concepts of cancer stem cells in head. Oct 11, 2012 the cancer stem cell csc concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they. 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. The cancer stem cell csc concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the.
Methods and protocols, preeminent researchers have compiled cancer stem cell research techniques and protocols to promote. The evolving concept of liver cancer stem cells kouki nio1,2, taro yamashita2 and shuichi kaneko2 abstract liver cancer is an often fatal malignant tumor with a high recurrence rate and chemoresistance. They could divide to produce both a regular cancer cell and a new stem cell. The cancer stem cell csc hypothesis assumes that a tumour is hierarchically organized and not all of the cells are equally capable of generating descendants, similarly to normal tissue. The cancer stem cell csc model has been established as a cellular mechanism that contributes to phenotypic and functional heterogeneity in diverse cancer types. These cells, termed cscs, comprise the top of the tumor cell hierarchy and have been isolated from many leukemias and solid tumors. As cscs are derived from tissue stem or progenitor cells, andor dedifferentiated mature cells, their signal transduction pathways are critical in the regulation of cscs.
The concept of cancer stem cells csc arose from the discovery that a majority of cells from some human leukemia acute myeloid leukemia, at different stages of differentiation, originated from transformed undifferentiated pluripotent stem cell. Oct 25, 2009 many articles have therefore investigated and discussed the hypothesis of stem cells of cancers. Cscs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma hnscc. The book also explores innovative therapeutic strategies in preclinical and clinical trials to target cancer stem. The major malignant phenotypes of cancer, including recurrence, metastasis, and chemoresistance, are related to the presence of cancer stem. Stem cells is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. A systematic literature analysis has shown that the presence of cscs, identified via the upregulation of stemness pathway biomarkers, results in reduced survival across all cancers studied. As shown, the traditional concept of a stem cell is of a discrete type of cell that belongs to a relatively homogeneous population of similar stem cells, that is identifiable by physical parameters, and that undergoes an irreversible loss of stem cell ability as it. The evolving concept of cancer and metastasis stem cells journal.
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