Tumor-derived PKCζ Represses The Migration Of Prostate Cancel Cells Through Macrophage-mediated Efferocytosis

Background and objectiveProstate cancer(PCa)is one of the most frequently occurring tumor among men worldwide.Thus,Expoloring effective treatment and finding new therapeutic targets is the current research hotspot for PCa.With the progress of research,the role of tumor microenvironment in prostate cancer has been gradually recognized.Tumor microenviroment(TME)is a complex microenvironment composed of tumor cells,various stromal cells,cytokines and other components.It is closely related to the occurrence and progression of tumor.Among them,tumor associated macrophages(TAMs)usually play a key role in tumor progression,and they are involved in the regulation of tumor progression through direct cell contact or secretion of cytokines.Recent studies have shown that macrophages clear apoptotic tumor cells in the tumor microenvironment called efferocytosis which regulate the polarization of macrophages and the release of inflammatory factors,thereby generating a tumor-promoting microenvironment and promoting immune escape of tumor cells.PKCζis a member of the protein kinase C(PKC)family and belongs to atypical PKC.It participates in and regulates different signal pathways in various tumors.Our previous study confirmed that PKCζ is a tumor suppressor of prostate cancer.However,it is not clear whether it affects tumor progression by regulating the tumor microenvironment.We test whether cancer-derived PKCζ in prostate cancer can regulate tumor progression by affecting the efferocytosis in the tumor environment.Furthermore,provide effective strategy for the treatment of Pea.Contents and methods1.The role of Pca-derived PKCζ on the efferocytosis in the prostate cancer microenvironmentRT-qPCR and Western Blotting were used to detect the overexpression of PKCζ.Cell counting kit 8 and transwell migration assay were performed to show the ability of the progression of prostate cancer cells.Fluorescently labled antibody of macrophage was used to detected the effectiveness of efferocytosis.2.The molecular mechanism of Pca-derived PKCζ regulates the efferocytosis and the mirgration of prostate cancer.RT-qPCR and Western Blotting were used to filter the moleculars which regulate the efferocytosis.Neutralizing antibody was performed to antagonize the expression of CD47 and further confirms the molecular mechanism of Pea-derived PKCζregulates the efferocytosis and the migration of prostate cancer cells.Results1.Expression of PKCζ in prostste cancer cells represses the efferocytosisImprove the expression of PKCζ in prostate cancer cells,weakening the ability of macrophage clear the apoptotic prostate cancer cells and repressing growth and migration of prostate cancer cells.2.Expression of PKCζ in prostste cancer cells represses the efferocytosis and cancer cell migration by regulating expression of CD47Inhibition the activity of CD47 in the prostate cancer cells,increase the ability of macrophage to clear apototic cancer cells as well as promote prostate cancer cells to migration.Conclusion1.Pca-derived PKCζ represses the efferocytosis in the prostate cancer microenvironment.2.Pca-derived PKCζ regulates the efferocytosis and cancer cell migration by enhangcing the expression of CD47.