An Organoid Assay for Long-Term Maintenance and Propagation of Mouse Prostate Luminal Epithelial Progenitors and Cancer Cells
Historically, prostate luminal epithelial progenitors and cancer cells have been difficult to culture, thus hampering the generation of representative models for the study of prostate homeostasis, epithelial lineage hierarchy relationship and cancer drug efficacy assessment. Here, we describe a newly developed culture methodology that can efficiently grow prostate luminal epithelial progenitors and cancer cells as organoids. Notably, the organoid assay favors prostate luminal cell growth, thus minimizing basal cell dominance upon the establishment and continuous propagation of prostate epithelial cells. Importantly, organoids cultured under this condition have demonstrated preservation of androgen responsiveness and intact androgen receptor signaling, providing a representative system to study castration resistance and androgen receptor independence.
Key wordsOrganoid culture Prostate luminal progenitors Prostate cancer Androgen receptor Genetically engineered mouse Castration resistance
We thank M. Shibata, S. Irshad, H.H. Zhu, M. Shen, W.Q. Gao, and members of the Chua lab (M.Y. Liu, Y. Zhang, X. Cai, and C.P. Liang) for insightful comments on the manuscript. This work was supported by grants from the National Natural Science Foundation of China (81672548 and 81874098 to C.W. Chua), the Program for Professor of Special Appointment (Eastern Scholar), the Shanghai Institutions of Higher Learning (2016012 to C.W. Chua), the State Key Laboratory of Oncogenes and Related Genes (90-17-01 to C.W. Chua), and the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20171917 to C.W. Chua).
Author Contributions: Together with M. Lei, C.W. Chua developed and optimized the organoid culture protocol in M. Shen’s lab at the Columbia University. C.W. Chua and Y. Shu wrote the book chapter manuscript, and prepared the tables as well as the figures that were adapted from original figures in Chua et al. .
- 9.Chua CW, Shibata M, Lei M, Toivanen R, Barlow LJ, Shen MM (2014) Culture of mouse prostate organoids. Protoc Exch. https://doi.org/10.1038/protex.2014.037