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Establishment and Characterization of a Human Adrenocortical Carcinoma Xenograft Model¹

Laboratoire d’Explorations Fonctionnelles Endocriniennes, INSERM U-515 (A.L., Y.L.B., C.G.), and Laboratoire d’Anatomie et Cytologie Pathologique (L.B.G.), Hôpital d’Enfants Armand Trousseau, 75012 Paris, France; Laboratoire de Biologie Hormonale, Hôpital Saint Louis (P.B.), 75010 Paris, France; and Service de Médecine Nucléaire (E.B., M.S.) and Laboratoire de Pharmacotoxicologie (G.V.), Institut Gustave Roussy, 96800 Villejuif, France

Address all correspondence and requests for reprints to: Dr. Christine Gicquel, Laboratoire d’Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, 26 avenue Arnold Netter, 75012 Paris, France. E-mail: christine.gicquel{at}trs.ap-hop-paris.fr

Adrenocortical carcinomas are rare malignant tumors. They have a poor prognosis, as they are often diagnosed late and are usually resistant to chemotherapy. The lack of a suitable animal model for these tumors has been a major obstacle to the evaluation of new therapeutic agents. The aim of this study was to establish and characterize xenografts of the human adrenocortical carcinoma NCI H295R cell line as a model of adrenocortical carcinoma for future therapeutic trials. This cell line was sc injected (6 x 10⁶ cells) into nude mice (n = 20). Solid tumors were locally measurable after 45 days at 90% of the inoculation sites. The xenografts were similar histologically to the original adrenocortical carcinoma from which the cell line was derived. The xenografts precisely reproduced the dysregulation of the insulin-like growth factor (IGF) system [overexpression of the IGF-II and IGF-binding protein-2 (IGFBP-2) genes] typical of adrenocortical carcinoma. Similarly to adrenocortical carcinomas, human IGFBP-2 (but not IGF-II) was secreted in mouse plasma. We analyzed steroid production (cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, ⁴-androstenedione, 11-deoxycortisol, corticosterone, and testosterone). Xenografts produced all three class of steroids, with the preferential production of androgens of the ⁴ pathway.

The H295R xenograft model is a good model of human adrenocortical carcinoma, as it mimics dysregulation of the IGF system usually found in these tumors. It also produces IGFBP-2 and steroids that can be used as tumor markers. This model may therefore be useful for evaluating therapeutic agents.

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