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
TLDR
The results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation.Abstract:
Recent observations indicate that, in several types of human cancer, only a phenotypic subset of cancer cells within each tumor is capable of initiating tumor growth. This functional subset of cancer cells is operationally defined as the “cancer stem cell” (CSC) subset. Here we developed a CSC model for the study of human colorectal cancer (CRC). Solid CRC tissues, either primary tissues collected from surgical specimens or xenografts established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, were disaggregated into single-cell suspensions and analyzed by flow cytometry. Surface markers that displayed intratumor heterogeneous expression among epithelial cancer cells were selected for cell sorting and tumorigenicity experiments. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. Our observations indicate that, in six of six human CRC tested, the ability to engraft in vivo in immunodeficient mice was restricted to a minority subpopulation of epithelial cell adhesion molecule (EpCAM)high/CD44+ epithelial cells. Tumors originated from EpCAMhigh/CD44+ cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Analysis of the surface molecule repertoire of EpCAMhigh/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. These results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation.read more
Citations
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Cancer stem cells in solid tumours: accumulating evidence and unresolved questions
TL;DR: The cancer stem cell (CSC) hypothesis provides an attractive cellular mechanism to account for the therapeutic refractoriness and dormant behaviour exhibited by many of these tumours.
Journal ArticleDOI
Tumour heterogeneity and cancer cell plasticity
TL;DR: Studies using lineage tracing and deep sequencing could have implications for the cancer stem-cell model and may help to determine the extent to which it accounts for therapy resistance and disease progression.
Journal ArticleDOI
Crypt stem cells as the cells-of-origin of intestinal cancer
Nick Barker,Rachel A. Ridgway,Johan H. van Es,Marc van de Wetering,Harry Begthel,Maaike van den Born,Esther Danenberg,Alan Richard Clarke,Owen J. Sansom,Hans Clevers +9 more
TL;DR: It is concluded that stem-cell-specific loss of Apc results in progressively growing neoplasia in long-lived intestinal stem cells.
Journal ArticleDOI
The cancer stem cell: premises, promises and challenges
TL;DR: This review attempts to summarize the underlying concepts of the notion that tumors are maintained by their own stem cells, to distinguish hard facts from beliefs and to define the future challenges of the field.
Journal ArticleDOI
Molecular Basis of Colorectal Cancer
TL;DR: This review gives an account of recent advances in the authors' knowledge of the molecular mechanisms in colorectal cancer.
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Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
Dominique Bonnet,John E. Dick +1 more
TL;DR: It is demonstrated that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) — termed the SCID leukemia-initiating cell, or SL-IC — possesses the differentiate and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell.
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A human colon cancer cell capable of initiating tumour growth in immunodeficient mice
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