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Int. J. Mol. Sci. 2019, 20(8), 1817; https://doi.org/10.3390/ijms20081817

Establishment and Characterization of 5-Fluorouracil-Resistant Human Colorectal Cancer Stem-Like Cells: Tumor Dynamics under Selection Pressure

1
McGowan Institute for Regenerative Medicine and Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
2
Ri.MED Foundation, 90133 Palermo, Italy
3
Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana 010000, Kazakhstan
*
Author to whom correspondence should be addressed.
Received: 28 February 2019 / Revised: 21 March 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
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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. View Full-Text
Keywords: colorectal cancer; chemoresistance; cancer stem cells colorectal cancer; chemoresistance; cancer stem cells
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Francipane, M.G.; Bulanin, D.; Lagasse, E. Establishment and Characterization of 5-Fluorouracil-Resistant Human Colorectal Cancer Stem-Like Cells: Tumor Dynamics under Selection Pressure. Int. J. Mol. Sci. 2019, 20, 1817.

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