Abstract 5000: Activin receptor subtype-2A regulates innate immune cell activation and non-canonical signaling in pancreatic cancer cells

Abstract More than 50% of all pancreatic cancer patients present with distant metastasis at the time of diagnosis highlighting the need for early biomarkers of pancreatic cancer progression. Inflammatory disorders of the pancreas increases the risk for developing pancreatic cancer suggesting an inflammatory component to disease initiation. Our research team has previously shown that activin A (activin), a critical inflammatory cytokine, contributes to pancreatitis development through activation of innate immune cells. Furthermore, activin co-localizes with pancreatic intraepithelial neoplasm (PanIN) lesions in a mouse model of inflammation assisted pancreatic ductal adenocarcinoma (PDAC). Here, we will test the hypothesis that activin is an early, targetable biomarker of PDAC. Western blots were performed to quantify pSMAD2/3, pERK, and PI3K on pancreatic cancer cells stimulated with activin in the presence/absence of anti-activin neutralizing antibody or a highly specific activin receptor subtype-2A (ACVR2A) inhibitor. qPCR was performed to quantify chemokine receptor expression in RAW264.7 macrophages and neutrophil-like HL-60 cells exposed to the same conditions. Transwell migration assays were performed on RAW264.6 macrophages exposed to conditioned media from pancreatic stellate cells treated with activin in the presence/absence of anti-activin neutralizing antibody or the ACVR2A inhibitor. Prelimindary data suggests ACVR2A regulates SMAD2/3 phosphorylation in pancreatic cancer cells. We also observed ACVR2A dependent increases in the migratory capacity of macrophages that was regulated via activin. Taken together, these data suggest activin mediates PDAC initiation and progression via activin-mediated ACVR2A signaling. Citation Format: Yuchen Wang, Mark B. Wiley, Jessica Bauer, Xinru Wang, Jordi Guillem-Marti, David Lee, David Baker, Barbara Jung. Activin receptor subtype-2A regulates innate immune cell activation and non-canonical signaling in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5000.