Dataset Information

A novel mouse model for liver metastasis of prostate cancer reveals dynamic tumour-immune cell communication.

ABSTRACT:

Objectives

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^f/f ;p53^f/f mice.

Materials and methods

PbCre⁺ ;rb1^f/f ;p53^f/f and PbCre⁺ ;pten^f/f ;p53^f/f 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.

Results

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.

Conclusions

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.

SUBMITTER: Liu K

PROVIDER: S-EPMC8249794 | biostudies-literature |

REPOSITORIES: biostudies-literature

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