B7-H3 Promotes Prostate Cancer Progression in Mice by Antagonizing Myeloid-Derived Suppressor Cell Apoptosis

Overview

Journal Technol Cancer Res Treat

Specialties Biomedical Engineering
Oncology
Pharmacology

Date 2020 Dec 7

PMID 33280506

Citations 5

Authors

Yunfen Zhou

Guangbo Zhang

Weijie Zhang

Xuedong Wei

Jianquan Hou

Yuhua Huang

Affiliations

Soon will be listed here.

Abstract

Background: B7-H3 is an important immunomodulatory molecule, and clinical studies have confirmed that its expression level is closely correlated with prostate cancer prognosis. However, the mechanism of its biological action is unclear.

Methods: An engineered cell line overexpressing B7-H3 was constructed. Cell apoptosis, growth and proliferation assays and an animal model were performed to analyze the role and possible mechanism of B7-H3 in promoting prostate cancer progression.

Results: Compared with the control cell line (Mock-RM-1), the B7-H3-overexpressing prostate cancer cell line (B7-H3-RM-1) showed no significant growth differences , whereas the tumorigenesis rate of B7-H3-RM-1 was significantly higher than that of Mock-RM-1. These results suggest that B7-H3indirectly, rather than directly, promotes prostate cancer progression. Further analysis revealed that significantly higher levels of myeloid-derived suppressor cells (MDSCs) accumulated in B7-H3-RM-1 tumor-bearing mice than in Mock-RM-1 mice. and experiments showed that B7-H3-RM-1 cells significantly antagonized MDSC apoptosis. To further confirm the role of MDSCs in B7-H3-mediated prostate cancer progression, model mice were pretreated with cyclophosphamide before inoculation to clear immune cells and achieve myelo suppression. The results showed no significant differences in tumor growth between the B7-H3-RM-1 group and the Mock-RM-1 group.

Conclusions: We found, for the first time, that B7-H3 can antagonize MDSC apoptosis, leading to MDSC accumulation in the tumor microenvironment and thereby promoting prostate cancer progression.

Citing Articles

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