Role of RGS10 in the ovarian cancer microenvironment

Ovarian cancer is the deadliest of gynecological cancers and is associated with a high rate of chemoresistance. The discovery of more effective treatments and new therapeutic targets in ovarian cancer requires disease models that better represent the tumor microenvironment and account for dynamic crosstalk between multiple cell types. Macrophages, one of the most abundant immune cells in the tumor microenvironment, are actively recruited into the tumor and can accelerate tumor progression and chemoresistance via the production of inflammatory mediators. Recently, our lab and others have established Regulator of G protein Signaling 10 as a key regulator of inflammatory signaling in both macrophages and ovarian cancer cells. RGS10 robustly regulates macrophage activation and polarization by suppressing the production of inflammatory cytokines TNF‐α and IL‐6. Further, RGS10 suppresses the activation of cyclooxygenase‐2 (COX2) expression in both ovarian cancer cells and macrophages. However, the regulatory role of RGS10 in the tumor microenvironment where macrophages and ovarian cancer cells have direct interaction has not been explored, and it is not known if RGS10 regulatory roles in these distinct cell types will be synergistic or oppositional. Further, RGS10’s role in cancer progression has not been investigated in an in vivo tumor xenograft model with an intact macrophage population. The current study employs both an in vitro co‐culture model of macrophages and ovarian cancer cell lines and an in vivo syngeneic ovarian tumor model using mouse ID8 ovarian cancer cells to define the role of RGS10 in inflammatory signaling between immune and tumor cells in the ovarian cancer microenvironment. Support or Funding Information Marsha Rivkin Foundation, University of Georgia