Abstract 4342: Loss of MSLN impairs pancreatic cancer growth in the peritoneal cavity

Abstract Mesothelin (MSLN) is a cell surface glycoprotein that is expressed in at least 85% of pancreatic adenocarcinoma but not on cells of the healthy pancreas nor in the parenchyma of other vital organs. Due to this differential expression, MSLN has been used as a target for various antibody based treatments and cancer vaccines. The physiologic role of MSLN is unknown. Previous reports have suggested that overexpression of MSLN may increase tumorigenicity and metastatic potential of pancreatic adenocarcinoma. To further define the role of MSLN in this disease, we deleted MSLN from the human pancreatic cancer cell line, KLM1, using CRISPR/Cas9 gene editing. Successful deletion of MSLN was confirmed via flow cytometry and immunoblotting. Furthermore, KLMΔMSLN cells were rendered invulnerable to the MSLN-targeted immunotoxin, RG7787, which depends on the presence of surface MSLN for cytotoxicity. In cell culture, KLMΔMSLN cells grew at the same rate as control cells. KLMΔMSLN formed subcutaneous tumors in nude mice with the same frequency as control cells and these tumors grew at the same rate. However, when nude mice were inoculated with KLMΔMSLN or control cells intraperitoneally, a marked decrease in tumor burden was observed in cells lacking MSLN. In summary, we have engineered a pancreatic cancer cell line that lacks MSLN and demonstrated that loss of MSLN impairs tumor growth and spread specifically within the peritoneal cavity. Further experiments are in progress to identify the factors contributing to this phenotype. Citation Format: Michael W. Rudloff, Danielle Arons, Salma El-Behaedi, Rakan Albalawy, Christine Alewine. Loss of MSLN impairs pancreatic cancer growth in the peritoneal cavity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4342. doi:10.1158/1538-7445.AM2017-4342