MP05-01 CHOLESTEROL METABOLISM REPROGRAMMING INDUCES THE SECRETION OF MDK TO PROMOTE M2 POLARIZATION OF MACROPHAGES AND PROMOTES THE PROGRESSION OF PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP05)1 May 2024MP05-01 CHOLESTEROL METABOLISM REPROGRAMMING INDUCES THE SECRETION OF MDK TO PROMOTE M2 POLARIZATION OF MACROPHAGES AND PROMOTES THE PROGRESSION OF PROSTATE CANCER Hai Huang and ShiRong Peng Hai HuangHai Huang and ShiRong PengShiRong Peng View All Author Informationhttps://doi.org/10.1097/01.JU.0001008740.27639.cc.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To reveal the phenomenon of cholesterol metabolism reprogramming during the occurrence and development of prostate cancer, and to explore the mechanism by which cholesterol metabolism reprogramming in prostate cancer cells promotes prostate cancer progression METHODS: Revealing changes in cholesterol synthesis, uptake, and content during the occurrence and development of prostate cancer through immunohistochemistry and cholesterol determination. Exploring the effect of cholesterol metabolism reprogramming in prostate cancer cells on the growth of prostate cancer using in vivo animal models. Add exogenous cholesterol to culture androgen-dependent prostate cancer cells, and evaluate the effect of cell supernatant on tumor-related macrophage polarization through cell immunofluorescence, flow cytometry, RT-qPCR, and protein immunoblotting. Detection of cytokines secreted in the supernatant of cholesterol metabolism reprogrammed prostate cancer cells and changes in downstream pathways of tumor-associated macrophages through proteomic analysis, RT qPCR, silver staining, and WB techniques. RESULTS: Immunohistochemical and cholesterol measurements indicate that the cholesterol content in prostate cancer tissue is higher than that in normal prostate tissue. During the development of prostate cancer, there is a cholesterol metabolism reprogramming dominated by increased cholesterol synthesis. Subcutaneous and in situ, tumor models of prostate cancer have confirmed that cholesterol accumulation in tumor tissue can promote the growth of prostate cancer. Cellular immunofluorescence, flow cytometry, RT qPCR, and Western blotting further confirmed that the supernatant of prostate cancer cells after cholesterol accumulation can promote M2 polarization of tumor-related macrophages, and M2 tumor-related macrophages further promote tumor cell growth. Proteomic analysis revealed that cholesterol accumulation induces the secretion of intermediate factor (Midkine) by prostate cancer cells, which binds to LRP1 on tumor-associated macrophages and activates the PI3K/AKT/ β-catenin pathway. CONCLUSIONS: This experimental study indicates that increased cholesterol synthesis is the main cause of cholesterol metabolism reprogramming and cholesterol accumulation during the occurrence and development of prostate cancer. Cholesterol accumulation induces tumor cells to secrete midkine, which binds to LRP1 on tumor-associated macrophages and activates the PI3K/AKT/β-catenin pathway promoting M2 polarization in tumor-associated macrophages. Source of Funding: This work was supported by the National key R&D plan of China (2022YFC3602904); the National Natural Science Foundation of China (No:81974395, No:82173036); Key R&D Plan of Guangdong Province (No: 2023B1111030006); International Science and technology cooperation project plan of Guangdong Province (No: 2021A0505030085); Sun Yat-Sen University Clinical Research 5010 Program (No: 2019005); Beijing Bethune Charitable Foundation (mnzl202001);Guangzhou Science and Technology Key R&D Project (202206010117); Beijing Xisike Clinical Oncology Research Foundation (Y-MSDZD2022-0760, Y-tongshu2021/ms-0162); Supported by the open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital to Hai Huang © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e43 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Hai Huang More articles by this author ShiRong Peng More articles by this author Expand All Advertisement PDF downloadLoading ...