A growth factor-reduced culture system for colorectal cancer organoids
Ronghui Tan, Ze Zhang, Peirong Ding, Yue Liu, Huidong Liu, Minyi Lu, Ye‐Guang Chen
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. • Establishment of a new growth factor-reduced culture system for long-term CRC organoid culture. • Establishment of a living biobank with 32 FASGN-cultured CRC organoids with tumor diversity. • FASGN-cultured CRC organoids preserve the histological, genetic features, and tumorigenicity of original tumors. • The Wnt-independence of CRC organoids correlates with gene mutations of the Wnt pathway.