Establishment and characterization of 5-fluorouracil-resistant human colorectal cancer stem-like cells: Tumor dynamics under selection pressure

Maria Giovanna Francipane, Denis Bulanin, Eric Lagasse

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

5-Fluorouracil (5-FU) remains the gold standard of first-line treatment for colorectal cancer (CRC). Although it may initially debulk the tumor mass, relapses frequently occur, indicating the existence of cancer cells that are therapy-resistant and are capable of refueling tumor growth. To identify mechanisms of drug resistance, CRC stem-like cells were subjected to long-term 5-FU selection using either intermittent treatment regimen with the IC50 drug dose or continuous treatment regimen with escalating drug doses. Parental cancer cells were cultivated in parallel. Real-time PCR arrays and bioinformatic tools were used to investigate gene expression changes. We found the first method selected for cancer cells with more aggressive features. We therefore transplanted these cancer cells or parental cells in mice, and again, found that not only did the 5-FU-selected cancer cells generate more aggressive tumors with respect to their parental counterpart, but they also showed a different gene expression pattern as compared to what we had observed in vitro, with ID1 the top upregulated gene. We propose ID1 as a stemness marker pervasively expressed in secondary lesions emerging after completion of chemotherapy.

Original languageEnglish
Article number1817
JournalInternational Journal of Molecular Sciences
Volume20
Issue number8
DOIs
Publication statusPublished - Apr 2 2019

Fingerprint

Neoplastic Stem Cells
stem cells
Fluorouracil
Tumors
Colorectal Neoplasms
tumors
cancer
Cells
Pressure
Neoplasms
Gene expression
drugs
gene expression
Pharmaceutical Preparations
Chemotherapy
Bioinformatics
dosage
refueling
Gene Expression
Genes

Keywords

  • Cancer stem cells
  • Chemoresistance
  • Colorectal cancer

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Establishment and characterization of 5-fluorouracil-resistant human colorectal cancer stem-like cells : Tumor dynamics under selection pressure. / Francipane, Maria Giovanna; Bulanin, Denis; Lagasse, Eric.

In: International Journal of Molecular Sciences, Vol. 20, No. 8, 1817, 02.04.2019.

Research output: Contribution to journalArticle

@article{bf4f0b1873bd404e9c3302934359e1b5,
title = "Establishment and characterization of 5-fluorouracil-resistant human colorectal cancer stem-like cells: Tumor dynamics under selection pressure",
abstract = "5-Fluorouracil (5-FU) remains the gold standard of first-line treatment for colorectal cancer (CRC). Although it may initially debulk the tumor mass, relapses frequently occur, indicating the existence of cancer cells that are therapy-resistant and are capable of refueling tumor growth. To identify mechanisms of drug resistance, CRC stem-like cells were subjected to long-term 5-FU selection using either intermittent treatment regimen with the IC50 drug dose or continuous treatment regimen with escalating drug doses. Parental cancer cells were cultivated in parallel. Real-time PCR arrays and bioinformatic tools were used to investigate gene expression changes. We found the first method selected for cancer cells with more aggressive features. We therefore transplanted these cancer cells or parental cells in mice, and again, found that not only did the 5-FU-selected cancer cells generate more aggressive tumors with respect to their parental counterpart, but they also showed a different gene expression pattern as compared to what we had observed in vitro, with ID1 the top upregulated gene. We propose ID1 as a stemness marker pervasively expressed in secondary lesions emerging after completion of chemotherapy.",
keywords = "Cancer stem cells, Chemoresistance, Colorectal cancer",
author = "Francipane, {Maria Giovanna} and Denis Bulanin and Eric Lagasse",
year = "2019",
month = "4",
day = "2",
doi = "10.3390/ijms20081817",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

TY - JOUR

T1 - Establishment and characterization of 5-fluorouracil-resistant human colorectal cancer stem-like cells

T2 - Tumor dynamics under selection pressure

AU - Francipane, Maria Giovanna

AU - Bulanin, Denis

AU - Lagasse, Eric

PY - 2019/4/2

Y1 - 2019/4/2

N2 - 5-Fluorouracil (5-FU) remains the gold standard of first-line treatment for colorectal cancer (CRC). Although it may initially debulk the tumor mass, relapses frequently occur, indicating the existence of cancer cells that are therapy-resistant and are capable of refueling tumor growth. To identify mechanisms of drug resistance, CRC stem-like cells were subjected to long-term 5-FU selection using either intermittent treatment regimen with the IC50 drug dose or continuous treatment regimen with escalating drug doses. Parental cancer cells were cultivated in parallel. Real-time PCR arrays and bioinformatic tools were used to investigate gene expression changes. We found the first method selected for cancer cells with more aggressive features. We therefore transplanted these cancer cells or parental cells in mice, and again, found that not only did the 5-FU-selected cancer cells generate more aggressive tumors with respect to their parental counterpart, but they also showed a different gene expression pattern as compared to what we had observed in vitro, with ID1 the top upregulated gene. We propose ID1 as a stemness marker pervasively expressed in secondary lesions emerging after completion of chemotherapy.

AB - 5-Fluorouracil (5-FU) remains the gold standard of first-line treatment for colorectal cancer (CRC). Although it may initially debulk the tumor mass, relapses frequently occur, indicating the existence of cancer cells that are therapy-resistant and are capable of refueling tumor growth. To identify mechanisms of drug resistance, CRC stem-like cells were subjected to long-term 5-FU selection using either intermittent treatment regimen with the IC50 drug dose or continuous treatment regimen with escalating drug doses. Parental cancer cells were cultivated in parallel. Real-time PCR arrays and bioinformatic tools were used to investigate gene expression changes. We found the first method selected for cancer cells with more aggressive features. We therefore transplanted these cancer cells or parental cells in mice, and again, found that not only did the 5-FU-selected cancer cells generate more aggressive tumors with respect to their parental counterpart, but they also showed a different gene expression pattern as compared to what we had observed in vitro, with ID1 the top upregulated gene. We propose ID1 as a stemness marker pervasively expressed in secondary lesions emerging after completion of chemotherapy.

KW - Cancer stem cells

KW - Chemoresistance

KW - Colorectal cancer

UR - http://www.scopus.com/inward/record.url?scp=85065289851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065289851&partnerID=8YFLogxK

U2 - 10.3390/ijms20081817

DO - 10.3390/ijms20081817

M3 - Article

C2 - 31013771

AN - SCOPUS:85065289851

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 8

M1 - 1817

ER -