Mouse ovarian cancer models recapitulate the human tumor microenvironment and patient response to treatment

Maniati, E. et al. (2020) Mouse ovarian cancer models recapitulate the human tumor microenvironment and patient response to treatment. Cell Reports, 30(2), 525-540.e7. (doi: 10.1016/j.celrep.2019.12.034) (PMID:31940494) (PMCID:PMC6963791)

Abstract

Although there are many prospective targets in the tumor microenvironment (TME) of high-grade serous ovarian cancer (HGSOC), pre-clinical testing is challenging, especially as there is limited information on the murine TME. Here, we characterize the TME of six orthotopic, transplantable syngeneic murine HGSOC lines established from genetic models and compare these to patient biopsies. We identify significant correlations between the transcriptome, host cell infiltrates, matrisome, vasculature, and tissue modulus of mouse and human TMEs, with several stromal and malignant targets in common. However, each model shows distinct differences and potential vulnerabilities that enabled us to test predictions about response to chemotherapy and an anti-IL-6 antibody. Using machine learning, the transcriptional profiles of the mouse tumors that differed in chemotherapy response are able to classify chemotherapy-sensitive and -refractory patient tumors. These models provide useful pre-clinical tools and may help identify subgroups of HGSOC patients who are most likely to respond to specific therapies.

• Item Type: Articles
• Additional Information: This project was funded by Cancer Research UK program grants A16354 and A25714 and ERC Advanced Grant ERC322566 (to F.R.B., C.B., G.G., P.K., A.L., R.M.D.-S., and O.M.T.P.); Cancer Research UK Career Establishment Award A27947 (to O.M.T.P.); Cancer Research UK core grant number A17196 (to O.J.S.); BBSRC CASE studentship BIDS3000032485 (to J.D.J.); Wellcome Trust Research Training Fellowship 20118/Z/16/Z (to O.H.); National Cancer Institute grant P50 CA228991; The Honorable Tina Brozman Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; The Claneil Foundation; the Basser Center for BRCA (to R.D.); and the European Commission (PCIG13-GA-2013-618174) (to R.P.). This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E (to L.S.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bailey, Dr Peter and Sansom, Professor Owen
• Authors: Maniati, E., Berlato, C., Gopinathan, G., Heath, O., Kotantaki, P., Lakhani, A., McDermott, J., Pegrum, C., Delaine-Smith, R. M., Pearce, O. M.T., Hirani, P., Joy, J. D., Szabova, L., Perets, R., Sansom, O. J., Drapkin, R., Bailey, P., and Balkwill, F. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Cell Reports 30(2): 525-540.e7
• Publisher Policy: Reproduced under a Creative Commons License