Original Articles: Basic ScienceOrthotopic murine xenograft model of uveal melanoma with spontaneous liver metastasisRamos, Raquela; Cabré, Eduarda; Vinyals, Antòniaa; Lorenzo, Danielb; Ferreres, Josep R.c; Varela, Mard; Gomá, Montsed; Paules, Maria Joséd; Gutierrez, Cristinae; Piulats, Josep M.f; Fabra, Àngelsa,*; Caminal, José M.b,* Author Information aOncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) bOphthalmology Department, Spanish Ocular Oncology National referal center (CSUR) and Ocular Translational Eye Research Unit, Hospital Universitari de Bellvitge (HUB)-IDIBELL cDermatology Department, Hospital Universitari de Bellvitge dPathology Department, Hospital Universitari de Bellvitge eRadiotherapy Department, Institut Catalá d’Oncologia (ICO), Hospital Duran Reynals fMedical Oncology, Institut Catalá d’Oncologia (ICO), Hospital Duran Reynals, Barcelona, Spain Received 17 May 2022 Accepted 6 September 2022 *Àngels Fabra and José M.Caminal contributed equally to the writing of the article. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to: Àngels Fabra, PhD, Idibell, Oncobell Program, Hospital Duran Reynals. Granvia de l’Hospitalet 199, L’Hospitalet de Llobregat, 08907, Spain, Tel: +34 60 086 5377; e-mail: [email protected] Melanoma Research 33(1):p 1-11, February 2023. | DOI: 10.1097/CMR.0000000000000860 Buy SDC Metrics Abstract Uveal melanoma is the most common intraocular malignancy in adults. Despite the effective primary treatment, up to 50% of patients with uveal melanoma will develop metastatic lesions mainly in the liver, which are resistant to conventional chemotherapy and lead to patient’s death. To date, no orthotopic murine models of uveal melanoma which can develop spontaneous metastasis are available for preclinical studies. Here, we describe a spontaneous metastatic model of uveal melanoma based on the orthotopic injection of human uveal melanoma cells into the suprachoroidal space of immunodeficient NSG mice. All mice injected with bioluminescent OMM2.5 (n = 23) or MP41 (n = 19) cells developed a primary tumor. After eye enucleation, additional bioluminescence signals were detected in the lungs and in the liver. At necropsy, histopathological studies confirmed the presence of lung metastases in 100% of the mice. Liver metastases were assessed in 87 and in 100% of the mice that received OMM2.5 or MP41 cells, respectively. All tumors and metastatic lesions expressed melanoma markers and the signaling molecules insulin-like growth factor type I receptor and myristoylated alanine-rich C-kinase substrate, commonly activated in uveal melanoma. The novelty of this orthotopic mouse xenograft model is the development of spontaneous metastases in the liver from the primary site, reproducing the organoespecificity of metastasis observed in uveal melanoma patients. The faster growth and the high metastatic incidence may be attributed at least in part, to the severe immunodeficiency of NSG mice. This model may be useful for preclinical testing of targeted therapies with potential uveal melanoma antimetastatic activity and to study the mechanisms involved in liver metastasis. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.