Establishment of a mouse xenograft model of metastatic adrenocortical carcinoma

// Aurelie Morin 1, 2 , Carmen Ruggiero 3, 4 , Estelle Robidel 1, 2 , Mabrouka Doghman-Bouguerra 3, 4 , Atze T. Das 5 , Remy Castellano 6 , Emmanuelle Josselin 6 , Judith Favier 1, 2 and Enzo Lalli 3, 4 1 Universite Paris Descartes, Sorbonne Paris Cite, Paris, France 2 Inserm UMR970, Paris Cardiovascular Research Centre, Paris, France 3 Universite Cote d’Azur, Valbonne, Sophia Antipolis, France 4 Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, Sophia Antipolis, France 5 Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 6 Aix Marseille University, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, France Correspondence to: Enzo Lalli, email: ninino@ipmc.cnrs.fr Keywords: adrenal cortex, cancer, cell lines, mouse models, xenografts Abbreviations: ACC, adrenocortical carcinoma; EMT, epithelial-mesenchymal transition; GFP, green fluorescent protein; HES, hematoxylin-eosin-safran; SF-1, Steroidogenic Factor 1 Received: December 08, 2016     Accepted: March 15, 2017     Published: April 07, 2017 ABSTRACT Adrenocortical carcinoma is a rare neoplasm with a poor prognosis. Very important advances have been made in the identification of the genetic determinants of adrenocortical carcinoma pathogenesis but our understanding is still limited about the mechanisms that determine cancer spread and metastasis. One major problem hindering preclinical experimentation for new therapies for adrenocortical carcinoma is represented by the lack of suitable animal models for metastatic disease. With the aim to overcome these limitations, in this study we tested several protocols in order to establish a mouse xenograft model of metastatic adrenocortical carcinoma. The most efficient method, based upon intrasplenic injection followed by splenectomy, produced metastases with high efficiency, whose development could be followed over time by bioluminescence measurements. We expect that the availability of this model will greatly improve the possibilities for preclinical testing of new treatments for advanced-stage disease.