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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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-FUresistant 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.

Original languageEnglish (US)
Pages (from-to)78698-78712
Number of pages15
JournalOncotarget
Volume7
Issue number48
DOIs
StatePublished - Jan 1 2016

Fingerprint

Neoplastic Stem Cells
Fluorouracil
Colonic Neoplasms
Phenotype
Gene Expression
Neoplasms

Keywords

  • 5-Fluorouracil
  • CD133
  • CD24
  • Colon cancer stem cells

ASJC Scopus subject areas

  • Oncology

Cite this

CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype. / Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Redd, Priscilla S.; Choi, Jeong Hyeon; Heaton, Christopher M.; Lee, Jeffrey R.; Nayak-Kapoor, Asha; Liu, Kebin.

In: Oncotarget, Vol. 7, No. 48, 01.01.2016, p. 78698-78712.

Research output: Contribution to journalArticle

Paschall, Amy V. ; Yang, Dafeng ; Lu, Chunwan ; Redd, Priscilla S. ; Choi, Jeong Hyeon ; Heaton, Christopher M. ; Lee, Jeffrey R. ; Nayak-Kapoor, Asha ; Liu, Kebin. / CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype. In: Oncotarget. 2016 ; Vol. 7, No. 48. pp. 78698-78712.
@article{e14c7214a097451daa1b2df5a68835c9,
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-FUresistant 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.",
keywords = "5-Fluorouracil, CD133, CD24, Colon cancer stem cells",
author = "Paschall, {Amy V.} and Dafeng Yang and Chunwan Lu and Redd, {Priscilla S.} and Choi, {Jeong Hyeon} and Heaton, {Christopher M.} and Lee, {Jeffrey R.} and Asha Nayak-Kapoor and Kebin Liu",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.12168",
language = "English (US)",
volume = "7",
pages = "78698--78712",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "48",

}

TY - JOUR

T1 - CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

AU - Paschall, Amy V.

AU - Yang, Dafeng

AU - Lu, Chunwan

AU - Redd, Priscilla S.

AU - Choi, Jeong Hyeon

AU - Heaton, Christopher M.

AU - Lee, Jeffrey R.

AU - Nayak-Kapoor, Asha

AU - Liu, Kebin

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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-FUresistant 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.

AB - 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-FUresistant 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.

KW - 5-Fluorouracil

KW - CD133

KW - CD24

KW - Colon cancer stem cells

UR - http://www.scopus.com/inward/record.url?scp=84998854583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84998854583&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.12168

DO - 10.18632/oncotarget.12168

M3 - Article

C2 - 27659530

AN - SCOPUS:84998854583

VL - 7

SP - 78698

EP - 78712

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 48

ER -