The Regulation of SLPI and its Impact on Metastasis and the Ovarian Tumor Microenvironment in Ovarian Cancer

Abstract

Understanding the factors that drive epithelial ovarian cancer progression is needed to design effective targeted therapies, especially knowing that it is the deadliest gynecological malignancy. SLPI is a protease inhibitor with anti-inflammatory properties and is highly expressed in ovarian cancers; however, its role in these cancers is unclear. This study found that Slpi expression was upregulated by MEK pathway signaling in mouse ovarian cancer cells. The effect of Slpi on ovarian cancer metastasis, survival, and the tumor microenvironment was also investigated. In suspension cultures, Slpi knockout cells formed smaller, more abundant aggregates than their Slpi-expressing controls, which correlated with increased metastases in vivo. Following intrabursal injections of Slpi-overexpressing and control cells, Slpi-overexpressing tumors exhibited reduced survival with fewer metastases, more macrophages, eosinophils, and dendritic cells. This research revealed that SLPI increases cancer aggressiveness by creating an immunosuppressive TME and promoting aggregation of metastatic cells.