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Phenotypic subpopulations of metastatic colon cancer stem cells: genomic analysis.
- Source :
-
Cancer genomics & proteomics [Cancer Genomics Proteomics] 2009 Jan-Feb; Vol. 6 (1), pp. 19-29. - Publication Year :
- 2009
-
Abstract
- Background: Human cancer is characterized by high heterogeneity in gene expression, varieties of differentiation phenotypes and tumor-host interrelations. Growing evidence suggests that tumor-initiating, or cancer stem cells (CSCs), may also represent a heterogeneous population. The present study was undertaken to isolate and characterize the different phenotypic subpopulations of metastatic colon cancer and to develop a working colon CSC model for obtaining highly tumorigenic and clonogenic cells in sufficient numbers.<br />Materials and Methods: Different phenotypic cell subpopulations were isolated based on differential levels and patterns of expression of several stemness markers, including CD133, CD44, CD166 and CD49b. Stemness properties of isolated cells were tested by analysis of their ability to form floating colonospheres in vitro, to induce tumors in NOD/SCID mice after transplantation at relatively low cell numbers, and to produce progenitors of different phenotypes.<br />Results: The metastatic colon cancer HCT116 cell line, which expressed a majority of known CSC markers, closely resembling the patterns of expression in exfoliated peritoneal cells from several metastatic colon cancer patients, was selected as a reference material. Genome-wide microarray analysis (Affymetrix; DAVID) of CD133(high) CSC-enriched versus CSC-depleted cell populations revealed 4,351 differentially expressed genes with an overrepresentation of those responsible for apoptosis resistance, regulation of cell cycle, proliferation, stemness and developmental pathways. Simultaneous analysis of 84 stem cell- and metastasis-related genes with corresponding PCR arrays identified genes differentially expressed in several colon CSC phenotypic populations versus bulk tumor cells, and in relation to each other. It was found that colonospheres induced by tumorigenic cells with the highest expression of CD133 and those which were induced by CD133/CD44-negative cells possessed profoundly different stem cell-related gene expression profiles.<br />Conclusion: The proposed approaches allow for reliable isolation and propagation of highly tumorigenic and clonogenic cells of different phenotypes. Genomic analysis of several candidate CSC phenotypic populations may contribute to the identification of novel targets for colon cancer stem cell-targeted drug development and treatment.
- Subjects :
- AC133 Antigen
Adenocarcinoma metabolism
Adenocarcinoma pathology
Animals
Antigens, CD genetics
Antigens, CD metabolism
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Colonic Neoplasms pathology
Gene Expression Regulation, Neoplastic
Glycoproteins genetics
Glycoproteins metabolism
Humans
Mice
Mice, Inbred NOD
Mice, Nude
Mice, SCID
Oligonucleotide Array Sequence Analysis
Peptides genetics
Peptides metabolism
Phenotype
Spheroids, Cellular pathology
Tumor Cells, Cultured
Colonic Neoplasms genetics
Gene Expression Profiling
Genome, Human
Neoplastic Stem Cells pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1109-6535
- Volume :
- 6
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer genomics & proteomics
- Publication Type :
- Academic Journal
- Accession number :
- 19451087