Joan F. Brozick

Murine cell lines with defined mutations model different histological subtypes of epithelial ovarian cancer

ABSTRACT Preclinical modeling of epithelial ovarian cancer in immune-competent mice progressing to orthotopic, spontaneous tumors is challenging, requiring multiple genetic modifications in the host. Transplantable models using cell lines are easier to implement than spontaneous animal models, given that they reproduce the key disease characteristics. To create new in vivo ovarian tumor models, we generated 28 murine ovarian cancer cell lines with distinct genetic traits, such as deletion of Trp53, activation of KrasG12D, or deletion of Pten or KrasG12D/Pten−/− combination. Two distinct Trp53 null cell lines recapitulate high-grade serous histology when orthotopically injected into immune-competent, syngeneic hosts. Cells with Pten deletion trigger high-grade endometrioid tumors, and cells with dual KrasG12D activation and Pten deletion model carcinosarcoma. The cells express different tumor antigens, secrete varying levels of cytokines and chemokines, and trigger tumors with diverse inflammation profiles and various intratumoral T- and B-lymphocyte infiltration patterns. RNA-sequencing data from 16 cell lines reveal the gene expression profile across distinct models with different histotypes. This versatile collection of murine cell lines supports translationally relevant studies in ovarian cancer.