Mast Cells Retard Tumor Growth in Ovarian Cancer: Insights from a Mouse Model

SIMPLE SUMMARY: Approximately 225,000 new cases of ovarian cancer are diagnosed annually worldwide, of which 140,000 die. The aim of the study was to assess the role of mast cells in ovarian cancer pathology. We confirmed a suppressive effect of mast cells on ovarian tumor growth both in vitro and in vivo. An accurate understanding of the interaction between immune defenses and malignant cells is of enormous importance for improving current treatments and establishing new ones against ovarian cancer. ABSTRACT: Ovarian cancer has the highest mortality rate among female reproductive tract malignancies. A complex network, including the interaction between tumor and immune cells, regulates the tumor microenvironment, survival, and growth. The role of mast cells (MCs) in ovarian tumor pathophysiology is poorly understood. We aimed to understand the effect of MCs on tumor cell migration and growth using in vitro and in vivo approaches. Wound healing assays using human tumor cell lines (SK-OV-3, OVCAR-3) and human MCs (HMC-1) were conducted. Murine ID8 tumor cells were injected into C57BL6/J wildtype (WT) and MC-deficient C57BL/6-Kit(W-sh/W-sh) (Kit(W-sh)) mice. Reconstitution of Kit(W-sh) was performed by the transfer of WT bone marrow-derived MCs (BMMCs). Tumor development was recorded by high-frequency ultrasonography. In vitro, we observed a diminished migration of human ovarian tumor cells upon direct or indirect MC contact. In vivo, application of ID8 cells into Kit(W-sh) mice resulted in significantly increased tumor growth compared to C57BL6/J mice. Injection of BMMCs into Kit(W-sh) mice reconstituted MCs and restored tumor growth. Our data show that MCs have a suppressive effect on ovarian tumor growth and may serve as a new therapeutic target.