Oncotarget

Research Papers:

CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

Amy V. Paschall, Dafeng Yang, Chunwan Lu, Priscilla S. Redd, Jeong-Hyeon Choi, Christopher M. Heaton, Jeffrey R. Lee, Asha Nayak-Kapoor, Kebin Liu _

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Abstract

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

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+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.

Author Information

Amy V. Paschall

Dafeng Yang

Chunwan Lu

Priscilla S. Redd

Jeong-Hyeon Choi

Christopher M. Heaton

Jeffrey R. Lee

Asha Nayak-Kapoor

Kebin Liu
Primary Contact  _


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