Stroma Secreted SPP1 in Tumor Microenvironment Accomplices in Ovarian Tumor Malignancy

Background: SPP1 is differentially expressed in various tumors. However, the function and expression of SPP1 in ovarian cancer remains unclear. Methods: Using TCGA, GTEx and GEO databases analysis that expression of SPP1 in ovarian cancer microenviroment. Through analysis on two GEO cohorts, TISIDB and TIMER database, and in vitro and in vivo experiments assessment correlation between SPP1 expression and the effects of immunosuppression by testing the infiltration and function of macrophage and neutrophil. The method of Kaplan-Meier plotter was analysed on correlation between SPP1 expression on ovarian cancer and overall survival or progression free survival. Findings: SPP1 is mainly expressed in ovarian cancer stroma. SPP1 expression was negatively associated with overall survival of ovarian cancer patients. SPP1 could enhance the adhesion, migration, and invasion of ovarian cancer cells through ITGA5 and ITGAV by in vitro experiments. TISIDB and TIMER database suggested that SPP1 expression was associated with immune cells infiltration, especially macrophage and neutrophil. Through analysis of two GEO cohorts, TISIDB and TIMER database, and animal experiments, activation of the NF-κB signal pathway in ovarian cancer stromal cells induces macrophage and neutrophil infiltration and promotes tumor development. In addition, higher spp1 protein level was considerably worse progression-free survival in our central, statistical analyses revealed that there was correlation between spp1 and NF-κB in tumor tissue. Interpretation: In sum, our results suggested that SPP1 influences mobility ability of ovarian cancer cells and created an immunosuppressive microenvironment. SPP1 may represent an excellent therapy target for ovarian cancer patients. Funding: This work was supported by the National Science Foundation of China (Nos. 81772491, Nos.81373433).Declaration of Interest: The authors have no conflict of interest.Ethical Approval: This study was performed with approval from the Committee on the Ethics of Animal Experiments in the Hubei province. All animal experiments were carried out in accordance with the Guide for the Care and Use of Laboratory Animals of Tongji Hospital in Hubei.