The OSUMMER lines: A series of ultraviolet-accelerated NRAS-mutant mouse melanoma cell lines syngeneic to C57BL/6.

Autor: Murphy BM; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Jensen DM; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA., Arnold TE; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA.; Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA., Aguilar-Valenzuela R; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA.; Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA., Hughes J; EMD Millipore Corporation, Temecula, California, USA., Posada V; Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA., Nguyen KT; Center for Genomic and Precision Medicine, Texas A&M Institute of Biosciences and Technology, Houston, Texas, USA., Chu VT; EMD Millipore Corporation, Temecula, California, USA., Tsai KY; Departments of Pathology and Tumor Biology, The H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA., Burd CJ; Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA., Burd CE; Department of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio, USA.; Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA.
Jazyk: angličtina
Zdroj: Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2023 Sep; Vol. 36 (5), pp. 365-377. Date of Electronic Publication: 2023 Jun 21.
DOI: 10.1111/pcmr.13107
Abstrakt: An increasing number of cancer subtypes are treated with front-line immunotherapy. However, approaches to overcome primary and acquired resistance remain limited. Preclinical mouse models are often used to investigate resistance mechanisms, novel drug combinations, and delivery methods; yet most of these models lack the genetic diversity and mutational patterns observed in human tumors. Here we describe a series of 13 C57BL/6J melanoma cell lines to address this gap in the field. The Ohio State University-Moffitt Melanoma Exposed to Radiation (OSUMMER) cell lines are derived from mice expressing endogenous, melanocyte-specific, and clinically relevant Nras driver mutations (Q61R, Q61K, or Q61L). Exposure of these animals to a single, non-burning dose of ultraviolet B accelerates the onset of spontaneous melanomas with mutational patterns akin to human disease. Furthermore, in vivo irradiation selects against potent tumor antigens, which could prevent the outgrowth of syngeneic cell transfers. Each OSUMMER cell line possesses distinct in vitro growth properties, trametinib sensitivity, mutational signatures, and predicted antigenicity. Analysis of OSUMMER allografts shows a correlation between strong, predicted antigenicity and poor tumor outgrowth. These data suggest that the OSUMMER lines will be a valuable tool for modeling the heterogeneous responses of human melanomas to targeted and immune-based therapies.
(© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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