Journal ArticleDOI
Cancer Stem Cells: Models and Concepts
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TLDR
The biological basis and the therapeutic implications of the stem cell model of cancer, first developed in human myeloid leukemias, is reviewed, which is today being extended to solid tumors, such as breast and brain cancer.Abstract:
Although monoclonal in origin, most tumors appear to contain a heterogeneous population of cancer cells. 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. An additional explanation, however, envisages human tumors not as mere monoclonal expansions of transformed cells, but rather as complex tridimensional tissues where cancer cells become functionally heterogeneous as a result of differentiation. 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. This model, first developed in human myeloid leukemias, is today being extended to solid tumors, such as breast and brain cancer. We review the biological basis and the therapeutic implications of the stem cell model of cancer.read more
Citations
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Journal ArticleDOI
Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer
Patrick C. Hermann,Stephan Huber,Tanja Herrler,Alexandra Aicher,Joachim W. Ellwart,Markus Guba,Christiane J. Bruns,Christopher Heeschen +7 more
TL;DR: It is demonstrated that a subpopulation of migrating CD133(+) CX CR4(+) cancer stem cells is essential for tumor metastasis and strategies aimed at modulating the SDF-1/CXCR4 axis may have important clinical applications to inhibit metastasis of cancer stem Cells.
Journal ArticleDOI
Phenotypic characterization of human colorectal cancer stem cells
Piero Dalerba,Scott J. Dylla,In-Kyung Park,Rui Liu,Xinhao Wang,Robert W. Cho,Timothy Hoey,Austin L. Gurney,Emina Huang,Diane M. Simeone,Andrew A. Shelton,Giorgio Parmiani,Chiara Castelli,Michael F. Clarke +13 more
TL;DR: The results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation.
Journal ArticleDOI
let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cells
Fengyan Yu,Fengyan Yu,Herui Yao,Pengcheng Zhu,Xiaoqin Zhang,Qiuhui Pan,Chang Gong,Yijun Huang,Xiaoqu Hu,Fengxi Su,Judy Lieberman,Erwei Song +11 more
TL;DR: Let-7 regulates multiple BT-IC stem cell-like properties by silencing more than one target, and miRNA expression in self-renewing and differentiated cells from breast cancer lines and in breast T-IC and non-BT-IC from 1 degrees breast cancers is compared.
Journal ArticleDOI
The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs
Ulrich F. Wellner,Jörg Schubert,Ulrike Burk,Otto Schmalhofer,Feng Zhu,Annika G Sonntag,Bettina Waldvogel,Corinne Vannier,Douglas S. Darling,Axel zur Hausen,Valerie G. Brunton,Jennifer P. Morton,Owen J. Sansom,Julia Schüler,Marc P. Stemmler,Christoph Herzberger,Ulrich T. Hopt,Tobias Keck,Simone Brabletz,Thomas Brabletz +19 more
TL;DR: It is proposed that ZEB1 links EMT-activation and stemness-maintenance by suppressingstemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells.
Journal ArticleDOI
Identification and characterization of ovarian cancer-initiating cells from primary human tumors.
Shu Zhang,Curt Balch,Michael W.Y. Chan,Hung Cheng Lai,Daniela Matei,Jeanne M. Schilder,Pearlly S. Yan,Tim H M Huang,Kenneth P. Nephew +8 more
TL;DR: It is asserted that epithelial ovarian cancers derive from a subpopulation of CD44(+)CD117(+) cells, thus representing a possible therapeutic target for this devastating disease.
References
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Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
A genetic model for colorectal tumorigenesis
Eric R. Fearon,Bert Vogelstein +1 more
TL;DR: A model for the genetic basis of colorectal neoplasia that includes the following salient features is presented, which may be applicable to other common epithelial neoplasms, in which tumors of varying stage are more difficult to study.
Journal ArticleDOI
Prospective identification of tumorigenic breast cancer cells
Muhammad Al-Hajj,Max S. Wicha,Adalberto Benito-Hernandez,Sean J. Morrison,Sean J. Morrison,Michael F. Clarke +5 more
TL;DR: The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival and strategies designed to target this population may lead to more effective therapies.
Journal ArticleDOI
Stem cells, cancer, and cancer stem cells
TL;DR: Stem cell biology has come of age: Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine.
Journal ArticleDOI
Identification of human brain tumour initiating cells
Sheila K. Singh,Cynthia Hawkins,Ian D. Clarke,Jeremy A. Squire,Jane Bayani,Takuichiro Hide,R. Mark Henkelman,Michael D. Cusimano,Peter B. Dirks +8 more
TL;DR: The development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo gives strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.
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