Establishment of highly metastatic ovarian cancer model with omental tropism via in vivo selection

Abstract

Epithelial ovarian cancer (OC) is often diagnosed at an advanced stage with peritoneal metastasis, and preclinical models mimicking the natural course of OC peritoneal metastasis are essential to improve treatment. We implanted ES2 and ID8 cells in the ovaries of mice and obtained highly metastatic (HM) sublines from their omental metastases after three cycles invivo selection. Orthotopic xenografts derived from the HM sublines showed enhanced omental tropism and more extensive metastasis with earlier onset. The HM cells exhibited increased invitro migration and invasion properties, and RNA sequencing revealed that the genes related to epithelial-mesenchymal transition and extracellular matrix regulation were significantly altered in the HM cells. Among them, the upregulated genes were significantly associated with poorer survival in OC patients. In conclusion, these HM sublines can be leveraged to establish spontaneous metastatic OC mouse models, which may serve as ideal preclinical models for anti-metastasis therapy for OC patients.