title: Genome and transcriptome profiles of CD133-positive colorectal cancer cells.
abstract: Colorectal carcinomas (CRC) might be organized hierarchically and contain a subpopulation of tumorigenic, putative cancer stem cells that are CD133 positive. We studied the biological and genetic characteristics of such cells in CRC cell lines and primary tumors. Three CRC cell lines were sorted in CD133 positive and negative fractions. The respective genetic aberration profiles were studied using array comparative genomic hybridization (aCGH) and expression profiling. Tumorigenicity for each cellular population was tested by injection into nude mice. Additionally, we compared CD133+ and CD133- cells of 12 primary colorectal tumors using laser capture microdissection and aCGH. Three of five CRC cell lines displayed both CD133+ and CD133- cells, but tumorigenicity of these subfractions did not differ significantly and aCGH revealed essentially identical genomic imbalances. However, 96 genes were differentially expressed between the two populations. Array comparative genomic hybridization analysis after laser capture microdissection of CD133+ and CD133- areas in primary colorectal tumors revealed genetic differences in 7 of 12 cases. The use of cell lines for studying genomic alterations that define cancer stem cell characteristics, therefore, seems questionable. In contrast, CD133+ cells in primary cancer samples showed a unique genomic aberration profile. In conclusion, our data suggest that CD133 positivity defines a genetically distinct cellular compartment in primary CRC, which potentially includes tumor initiating cells.
authors: Section of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Timo
authors: T
authors: Gaiser
authors: Jordi
authors: J
authors: Camps
authors: Sandra
authors: S
authors: Meinhardt
authors: Danny
authors: D
authors: Wangsa
authors: Quang Tri
authors: QT
authors: Nguyen
authors: Sudhir
authors: S
authors: Varma
authors: Claudia
authors: C
authors: Dittfeld
authors: Leoni A
authors: LA
authors: Kunz-Schughart
authors: Ralf
authors: R
authors: Kemmerling
authors: Maria R
authors: MR
authors: Becker
authors: Kerstin
authors: K
authors: Heselmeyer-Haddad
authors: Thomas
authors: T
authors: Ried
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001706:Biopsy / Q000379:methods; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D005434:Flow Cytometry / Q000379:methods; D016678:Genome; D023281:Genomics / Q000379:methods; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007834:Lasers; D051379:Mice; D008819:Mice, Nude; D042282:Microdissection; D009368:Neoplasm Transplantation; D010455:Peptides; D014158:Transcription, Genetic
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse