Chen, J., Guo, T., Zhang, L., Qin, L. X., Singer, S., Maki, R. G., Taguchi, T., Dematteo, R., Besmer, P., Antonescu, C. R. (February 2012) CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers. Genes Chromosomes Cancer, 51 (2). pp. 186-95. ISSN 1098-2264 (Electronic)1045-2257 (Linking)
Abstract
Although imatinib mesylate has been a major breakthrough in the treatment of advanced gastrointestinal stromal tumors (GIST), complete responses are rare and most patients eventually develop resistance to the drug. Thus, the possibility of an imatinib-insensitive cell subpopulation within GIST tumors, harboring stem cell characteristics, may be responsible for the clinical failures. However, the existence of a cancer stem cell component in GIST has not been yet established. This study was aimed to determine whether expression of commonly used stem cell markers in other malignancies, that is, CD133 and CD44, might identify cells with characteristics of cancer stem/progenitor cells in human GIST. CD133 and CD44 expression in GIST explants was analyzed by flow cytometry, immunofluorescence, and gene expression. Their transcription levels were correlated with clinical and molecular factors in a large, well-annotated cohort of GIST patients. FACS sorted GIST cells based on CD133 and CD44 expression were isolated and used to assess phenotypic characteristics, ability to maintain their surface expression, sensitivity to imatinib, and expression signature. The enrichment in CD133/CD44 cells in the side population (SP) assay was also investigated. CD133 expression was consistently found in GIST. CD133(-) cells formed more colonies, were more invasive in a matrigel assay, and showed enrichment in the SP cells, compared to CD133(+) cells. CD133 expression was also detected in the two imatinib-sensitive GIST cell lines, while was absent in the imatinib-resistant lines. Our results show that CD133 and CD44 are universally expressed in GIST, and may represent a lineage rather than a cancer stem cell marker.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Adolescent Adult Antigens, CD/genetics/*metabolism Antigens, CD44/genetics/*metabolism Biomarkers, Tumor/genetics/*metabolism Cell Line, Tumor Cell Proliferation Child Child, Preschool Gastrointestinal Neoplasms/genetics/*metabolism/pathology Gastrointestinal Stromal Tumors/genetics/*metabolism/pathology Gene Expression Gene Expression Profiling Glycoproteins/genetics/*metabolism Humans Infant Neoplastic Stem Cells/*metabolism Peptides/genetics/*metabolism Sarcoma/genetics/metabolism Side-Population Cells/metabolism Up-Regulation Young Adult |
| Subjects: | diseases & disorders > cancer diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | February 2012 |
| Date Deposited: | 20 Oct 2016 18:55 |
| Last Modified: | 20 Oct 2016 18:55 |
| PMCID: | PMC3366284 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33729 |
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