CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype
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Amy V. Paschall1,2,3, Dafeng Yang1,3, Chunwan Lu1,3, Priscilla S. Redd1,2,3, Jeong-Hyeon Choi2, Christopher M. Heaton3, Jeffrey R. Lee3, Asha Nayak-Kapoor2,3, Kebin Liu1,2,3
1Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
2Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
3Charlie Norwood VA Medical Center, Augusta, GA 30904, USA
Kebin Liu, email: Kliu@augusta.edu
Keywords: CD133, CD24, colon cancer stem cells, 5-Fluorouracil
Received: January 14, 2016 Accepted: September 12, 2016 Published: September 21, 2016
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.
Amy V. Paschall
Priscilla S. Redd
Christopher M. Heaton
Jeffrey R. Lee
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