In contrast to extensive studies on bone metastasis in advanced prostate cancer (PCa), liver metastasis has been under-researched so far. In order to decipher molecular and cellular mechanisms underpinning liver metastasis of advanced PCa, we develop a rapid and immune sufficient mouse model for liver metastasis of PCa via orthotopic injection of organoids from PbCre ; rb1 ;p53 mice.
PbCre ;rb1 ;p53 and PbCre ;pten ;p53 mice were used to generate PCa organoid cultures in vitro. Immune sufficient liver metastasis models were established via orthotopic transplantation of organoids into the prostate of C57BL/6 mice. Immunofluorescent and immunohistochemical staining were performed to characterize the lineage profile in primary tumour and organoid-derived tumour (ODT). The growth of niche-labelling reporter infected ODT can be visualized by bioluminescent imaging system. Immune cells that communicated with tumour cells in the liver metastatic niche were determined by flow cytometry.
A PCa liver metastasis model with full penetrance is established in immune-intact mouse. This model reconstitutes the histological and lineage features of original tumours and reveals dynamic tumour-immune cell communication in liver metastatic foci. Our results suggest that a lack of CD8 T cell and an enrichment of CD163 M2-like macrophage as well as PD1 CD4 T cell contribute to an immuno-suppressive microenvironment of PCa liver metastasis.
Our model can be served as a reliable tool for analysis of the molecular pathogenesis and tumour-immune cell crosstalk in liver metastasis of PCa, and might be used as a valuable in vivo model for therapy development.
© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
About The Expert
Kaiyuan Liu
Na Jing
Deng Wang
Penghui Xu
Jinming Wang
Xinyu Chen
Chaping Cheng
Zhixiang Xin
Yuman He
Huifang Zhao
ZhongZhong Ji
Pengcheng Zhang
Wei-Qiang Gao
Helen He Zhu
Kai Zhang
References
PubMed