A growth factor-reduced culture system for colorectal cancer organoids

Cancer Lett. 2024 Apr 28:588:216737. doi: 10.1016/j.canlet.2024.216737. Epub 2024 Feb 19.

Abstract

Although organoids derived from tumor tissues have been widely used in cancer research, it is a great challenge for cultured organoids to retain the characteristics of the original tumor tissues due to their heterogeneity. In this study, we explore organoid culture recipes to capture tumor features of colorectal cancers. We find that the activation of Wnt and EGF signaling and inhibition of BMP signaling are non-essential for the survival of most colorectal cancer organoids (CRCOs). We design a growth factor-reduced culture medium containing FGF10, A83-01 (TGF-β type I receptor inhibitor), SB202190 (p38 MAPK inhibitor), gastrin, and nicotinamide. Using this medium, we can maintain tumor features in long-term CRCO cultivation, as evidenced by histopathology, genetic stability, tumorigenicity, and response of clinical treatments. Our findings offer a reliable and economical strategy for CRCO culture, facilitating the utilization of organoids in colorectal cancer research and treatment.

Keywords: Colorectal cancer; Culture system; Drug sensitivity; Organoids; Tumorigenesis.

MeSH terms

  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Organoids / pathology
  • Signal Transduction*

Substances

  • Intercellular Signaling Peptides and Proteins