Establishment of novel murine cell lines with defined mutations for preclinical in vitro and in vivo investigations of syngeneic epithelial ovarian cancer with different histological subtypes and inflammatory profiles
Preclinical modeling of epithelial ovarian cancer in immune competent mice progressing to spontaneous tumors is challenging, requiring multiple genetic modifications in the host. We have generated a total of 28 immortalized cell lines with distinct genetic traits. Primary OSE cells were propagated in vitro and reached immortalization after an average of 8-10 months in culture. The cells were further engineered via deletion of Trp53, activation of oncogenic KrasG12D, deletion of Pten tumor suppressor or KrasG12D/Pten-/- combination. Cellular transformation was confirmed in vivo, via orthotopic tumor growth syngeneic hosts. Two different Trp53 null cell lines recapitulate high grade serous histology, Pten deletion triggers aggressive, high grade endometrioid tumors, and cells with dual KrasG12D activation and Pten deletion model carcinosarcoma. The cells express different tumor antigens, secrete various levels of chemoattracting cytokines and chemokines and trigger diverse in vivo inflammation profiles, including intratumoral T and B lymphocyte conglomerates. RNAseq data from 16 cell lines reveal the gene expression profile of several distinct models for high grade serous, endometrioid and carcinosarcoma histotypes. This versatile collection of murine cell lines significantly broadens the preclinical modeling capacity in ovarian cancer. Overall design: Comparative gene expression profiling analysis of RNA-seq data for 28 immortalized and/or transformed mouse ovarian cell lines and some reference cell lines (2F8,2F8cis, ID8, and ID8-VEGF).