Abstract B34: Defining an orthotopic, syngeneic metastatic melanoma model for characterizing the immunotherapeutic activity of the prostamide, 15dPMJ2

Abstract

Abstract Metastatic melanoma (MM) is the deadliest form of skin cancer in the United States, with one person dying from the disease every hour. Metastasis occurs when cells from the primary tumor enter the systemic circulation and grow at local and distant organ sites. The most common sites of melanoma metastasis are the lymph nodes, bone, brain, and lungs. Melanoma that has metastasized is not effectively treated with cytotoxic therapeutics that are currently available, although immunotherapeutic and targeted agents produce more favorable outcomes. Despite the availability of these effective agents, MM is still associated with high mortality rates. In order to develop new and highly effective agents that robustly eliminate MM, current models of metastatic disease in immunocompetent animals must be improved. Several in vivo models, including those that look at endocannabinoids and their metabolites, focus on injecting tumor cells directly into the circulation via the tail vein to allow lesions to form within the lungs. While these models permit rapid metastasis at relevant sites, they lack primary tumor formation and therefore do not mimic the clinical disease. Other MM models employ subcutaneous tumor inoculation to permit primary tumors to spontaneously metastasize. However, the subcutaneous space is not an orthotopic site for melanoma. Therefore, well-established models of spontaneous metastasis from orthotopic sites must be improved to more accurately recapitulate MM and study the effect of endocannabinoids and their metabolites in this disease. The goal of the current study is to modify an existing syngeneic, orthotopic model of spontaneous MM to more precisely reproduce clinical features of metastasis. In this model, B16F10 melanoma cells that expressed firefly luciferase were inoculated on the dorsal ear of C57BL/6 mice. Spontaneous metastasis was then facilitated by removing the primary lesion to prolong the duration before humane endpoints were reached. Metastatic tumor formation in the draining lymph node and at distant sites was observed by using the IVIS Lumina imaging system and by gross examination of target organs after euthanasia. According to our preliminary data, primary tumors developed after an average of 2-3 weeks and metastatic lesions formed in the draining lymph node approximately 8 weeks after inoculation. Phenotypic characteristics that served as markers of metastasis and determinants of primary tumor removal were also identified. Histopathologic analysis of the primary and metastatic tumors revealed that the morphologic appearance of the lesions was consistent with patient melanoma. Further optimization of this model will allow us to mimic MM more precisely. Animal tumor models with greater translational value will provide a more comprehensive understanding of the metastatic process and, ultimately, the effects of endocannabinoids and their metabolites in MM. Citation Format: Rukiyah T. Van Dross, Ariel Myers, Kathleen Thayne. Defining an orthotopic, syngeneic metastatic melanoma model for characterizing the immunotherapeutic activity of the prostamide, 15dPMJ2 [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B34.