CD133 + CD24 lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

// Amy V. Paschall 1, 2, 3 , Dafeng Yang 1, 3 , Chunwan Lu 1, 3 , Priscilla S. Redd 1, 2, 3 , Jeong-Hyeon Choi 2 , Christopher M. Heaton 3 , Jeffrey R. Lee 3 , Asha Nayak-Kapoor 2, 3 , Kebin Liu 1, 2, 3 1 Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA 2 Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA 3 Charlie Norwood VA Medical Center, Augusta, GA 30904, USA Correspondence to: 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 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 + CD24 lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133 + CD24 lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells.