title: CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype.
abstract: The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.|Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Paschall
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Dafeng
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Chunwan
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.|Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Priscilla S
authors.initials: PS
authors.lastname: Redd
authors.affiliation: Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Heaton
authors.affiliation: Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Nayak-Kapoor
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.|Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: Kebin
authors.initials: K
authors.lastname: Liu
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D059467:Transcriptome
chemical_list: D000071916:AC133 Antigen; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C000606023:PROM1 protein, human; D000444:Aldehyde Dehydrogenase; D005472:Fluorouracil
keywords: 5-Fluorouracil; CD133; CD24; colon cancer stem cells