ID8 cells manifest phenotypic plasticity and molecular heterogeneity of high-grade serous ovarian cancer in response to the local tissue niche

Spontaneously transformed mouse ovarian surface epithelial cell line ID8 generates a syngeneic mouse model, frequently used in pre-clinical evaluation. Towards a precise, subtype-specific perspective of such applications, we thought it pertinent to study its stratification into a specific molecular subtype, which would provide an accurate setting for interpretation of experimental data. Stratification of ID8 model was achieved through phenotypic, histopathological, and molecular assessment of ID8 cells grown in vitro, its primary xenografts and metastases. TME investigation of primary and metastatic tumors revealed contrasting immune populations. Overall design: Stratification was performed on ID8 cell line and ID8 generated xenografts based on immunostaining, live cell imaging, histopathology and transcriptomics and proteomics. TME investigation for each xenograft was done through flow cytometry analysis.ID8 cells present E/M phenotype. Phenotypic plasticity retention in them causes class switching of ID8 cells in response to niche alteration, from E/M (in culture) to intermediate epithelial (iE) in orthotopic tumors while intermediate mesenchymal (iM) in subcutaneous tumors. Metastasis of ID8 primary tumor resulted into differentiated mesenchymal phenotype in ascites while differentiated epithelial phenotype in secondary intestinal tumors. Immune profiling of primary and secondary xenografts revealed differences in immune repertoire of tumors, highlighting subcutaneous tumor model to be inappropriate as compared to orthotopic model.