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⁺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.