title: Establishment and Characterization of Orthotopic Mouse Models for Human Uveal Melanoma Hepatic Colonization.
abstract: Uveal melanoma (UM) is a rare type of melanoma, although it is the most common primary ocular malignant tumor in adults. Nearly one-half the patients with primary UM subsequently develop systemic metastasis, preferentially to the liver. Currently, no treatment is effective for UM hepatic metastasis, and the prognosis is universally poor. The main challenge in designing a treatment strategy for UM hepatic metastasis is the lack of suitable animal models. We developed two orthotopic mouse models for human UM hepatic metastases: direct hepatic implantation model (intrahepatic dissemination model) and splenic-implantation model (hematogenous dissemination model) and investigated the tumorgenesis in the liver. A human UM cell line, established from a hepatic metastasis and nonobese diabetic severe combined immunodeficient γ mice, were used for development of in vivo tumor models. In the direct hepatic implantation model, a localized tumor developed in the liver in all cases and intrahepatic dissemination was subsequently seen in about one-half of cases. However, in the splenic implantation model, multiple hepatic metastases were observed after splenic implantation. Hepatic tumors subsequently seeded intra-abdominal metastasis; however, lung metastases were not seen. These findings are consistent with those observed in human UM hepatic metastases. These orthotopic mouse models offer useful tools to investigate the biological behavior of human UM cells in the liver.
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Breast Surgery, National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, Kure-shi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ozaki
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Raja
authors.initials: R
authors.lastname: Vuyyuru
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Ken
authors.initials: K
authors.lastname: Kageyama
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Mizue
authors.initials: M
authors.lastname: Terai
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohara
authors.affiliation: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Hanyin
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Tim
authors.initials: T
authors.lastname: Manser
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mastrangelo
authors.affiliation: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Aplin
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: takami.sato@jefferson.edu.
authors.forename: Takami
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000556:secondary*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods; D014604:Uveal Neoplasms / Q000556:secondary*; D000098943:Uveal Melanoma