Abstract 1329: Aging increases malignant peritoneal mesothelioma metastasis

Abstract

Abstract Mesothelioma is a rare cancer with approximately 3,000 new cases each year. There are three types of mesotheliomas including pleural (75%), pericardial (>1%) and peritoneal (20%). Mesothelioma occurs in the mesothelial cells, which form a protective barrier to multiple organs. Malignant peritoneal mesothelioma (MPM) is initiated in the peritoneum, a serous membrane that lines the inner walls of the abdominal cavity and the outside of the visceral organs and is a very receptive environment for malignancy and metastasis. MPM metastasizes to the abdominal cavity, affecting the omentum, liver, stomach, intestines, and kidneys. MPM is extremely difficult to diagnose due to its vague symptoms, such as abdominal distension, abdominal pain, weight loss, and nausea. Due to difficulty in diagnosis, most patients are diagnosed at an advanced disease (stage III or IV) with a very poor prognosis with a 9% 5-year survival rate. Asbestos exposure is a major risk factor for MPM with symptoms taking 20-50 years post- exposure to appear, making MPM prominent in aged adults. Mesothelin (MSLN), a 40 kDa protein, is normally expressed on the surface of mesothelial cells and manifests at abnormally high levels in several carcinomas including malignant peritoneal mesothelioma. The exact role of mesothelin is not yet fully understood as mesothelin knockout mice do not display an abnormal phenotype. However, there is some evidence to suggest that mesothelin is involved in tumor cell adhesion by binding to the tumor antigen MUC16. Mesothelin wild-type (WT) and knockout (KO) mice were used to investigate the role of host mesothelin expression on MPM metastasis. A MPM cell line was tagged with nuclear red fluorescence protein (RFP) and injected into the abdomen of female C57Bl/6, young (3-6 months) and aged (18-23 months), MSLN WT or KO mice. Disease progression was evaluated post injection of tumor cells by fluorescent in vivo imaging prior to end point dissection. The abdominal cavity was imaged in situ and tumor burden was evaluated using Image J. Overall, aged mice had increased abdominal tumor burden regardless of host MSLN expression. Aged MSLN KO mice displayed an increase in abdominal tumor burden compared to aged MSLN WT mice, however this difference was not significant. Interestingly, the immune profile of the abdominal cavity of tumor naive mice displays a decrease in natural killer (NK) cells and peritoneal macrophages in aged mice suggesting a role in regulating metastatic peritoneal mesothelioma and could possibly be targets for new immunotherapies. This study demonstrates host age increases tumor growth and metastatic success in peritoneal mesothelioma. Citation Format: Mykayla Miller. Aging increases malignant peritoneal mesothelioma metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1329.