Patient-Derived Colorectal Cancer Organoids Upregulate Revival Stem Cell Marker Genes following Chemotherapeutic Treatment

Rebekah M. Engel, Wing Hei Chan, David Nickless, Sara Hlavca, Elizabeth Richards, Genevieve Kerr, Karen Oliva, Paul J. McMurrick, Thierry Jarde, Helen E. Abud

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Colorectal cancer stem cells have been proposed to drive disease progression, tumour recurrence and chemoresistance. However, studies ablating leucine rich repeat containing G protein-coupled receptor 5 (LGR5)-positive stem cells have shown that they are rapidly replenished in primary tumours. Following injury in normal tissue, LGR5+ stem cells are replaced by a newly defined, transient population of revival stem cells. We investigated whether markers of the revival stem cell population are present in colorectal tumours and how this signature relates to chemoresistance. We examined the expression of different stem cell markers in a cohort of patient-derived colorectal cancer organoids and correlated expression with sensitivity to 5-fluorouracil (5-FU) treatment. Our findings revealed that there was inter-tumour variability in the expression of stem cell markers. Clusterin (CLU), a marker of the revival stem cell population, was significantly enriched following 5-FU treatment and expression correlated with the level of drug resistance. Patient outcome data revealed that CLU expression is associated with both lower patient survival and an increase in disease recurrence. This suggests that CLU is a marker of drug resistance and may identify cells that drive colorectal cancer progression.
Original languageEnglish
Article number128
Number of pages13
JournalJournal of Clinical Medicine
Volume9
Issue number1
DOIs
Publication statusPublished - 2 Jan 2020

Keywords

  • bowel cancer
  • organoid
  • tumoroid
  • colorectal
  • colon
  • stem cell
  • chemotherapy resistance

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