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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2023

Open Access 31-07-2023 | Colorectal Cancer | Translational Research

Cancer Stem Cells Persist Despite Cellular Damage, Emergence of the Refractory Cell Population

Authors: Ayumi Nagae, MD, Norikatsu Miyoshi, MD, PhD, Shiki Fujino, MD, PhD, Masafumi Horie, MD, PhD, Shinichi Yachida, MD, PhD, Masaru Sasaki, MD, PhD, Yuki Sekido, MD, PhD, Tsuyoshi Hata, MD, PhD, Atsushi Hamabe, MD, PhD, Takayuki Ogino, MD, PhD, Hidekazu Takahashi, MD, PhD, Mamoru Uemura, MD, PhD, Hirofumi Yamamoto, MD, PhD, Yuichiro Doki, MD, PhD, Hidetoshi Eguchi, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2023

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Abstract

Purpose

Cancer stem cells (CSCs) are responsible for chemotherapy resistance and have unique properties that protect them from chemotherapy. Investigating CSCs may help to identify the population that is more resistant to treatments, leading to recurrence. We evaluated persisting CSCs, emerging after chemotherapy that cause tumor recurrence.

Methods

Using human colorectal cancer organoids prepared from surgical specimens, we looked at changes in CSCs, the emergence and changes in the original population, which single-cell analysis identified.

Results

With regards to changes in cancer stem cell markers, CD44 showed low levels after 5-fluorouracil administration. Once the CD44-ve population was sorted and cultured, the CD44+ve population gradually emerged, and the CD44-ve population decreased. Compared with the CD44-ve population of an organoid parent, the CD44-ve population proliferated after chemotherapeutic agent stimulation. The CD44-ve population was derived from the CD44+ve population before chemotherapeutic agents. In addition, when the CD44 variants were evaluated, the CD44v9 population remained. In single-cell analysis, we found that POU5F1 was highly expressed in the CD44low population. Velocity analysis showed that the CD44-ve population was induced after chemotherapy and expressed POU5F1. POU5F1-EGFP-Casp9 transfected organoids resulted in the appearance of a CD44-ve population after administration of a chemotherapeutic reagent. Both in vivo and in vitro, the dimerizer administration inhibited tumor growth significantly.

Conclusions

POU5F1 is involved in chemotherapy resistance in relation to stemness. For the treatment against refractory tumors, such as the recurrence after chemotherapy, the treatment should target the emerging specific population such as CD44 (or CD44v9) and proliferative cancer cells.
Appendix
Available only for authorised users
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Metadata
Title
Cancer Stem Cells Persist Despite Cellular Damage, Emergence of the Refractory Cell Population
Authors
Ayumi Nagae, MD
Norikatsu Miyoshi, MD, PhD
Shiki Fujino, MD, PhD
Masafumi Horie, MD, PhD
Shinichi Yachida, MD, PhD
Masaru Sasaki, MD, PhD
Yuki Sekido, MD, PhD
Tsuyoshi Hata, MD, PhD
Atsushi Hamabe, MD, PhD
Takayuki Ogino, MD, PhD
Hidekazu Takahashi, MD, PhD
Mamoru Uemura, MD, PhD
Hirofumi Yamamoto, MD, PhD
Yuichiro Doki, MD, PhD
Hidetoshi Eguchi, MD, PhD
Publication date
31-07-2023
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2023
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-023-13849-x

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