Identification of a novel IL-5 signaling pathway in chronic pancreatitis and crosstalk with pancreatic tumor cells

• DOI: 10.1186/s12964-020-00594-x
• Publication Date: 2020-06-17T12:02:58Z
• Authors: Sarah B. Gitto; Jordan M. Beardsley; Sai Preethi Nakkina; Jeremiah L. Oyer; Kathryn A. Cline; Sally A. Litherland; Alicja J. Copik; Amr S. Khaled; Na’im Fanaian; J. Pablo Arnoletti; Deborah A. Altomare
• Keywords: Crosstalk

While inflammation is associated with pancreatic cancer, the underlying mechanisms leading to cancer initiation are still being delineated. Eosinophils may promote or inhibit tumor growth, although specific role in has yet be determined. Eosinophil-supporting cytokine interleukin-5 and receptor likely have a role, but significance microenvironment unknown.Genetically engineered Akt1Myr/KRasG12D KRasG12D mice were used model changes induced by chronic inflammation. Tissue samples collected analyze infiltration of immune cells, whereas serum was amylase activity inflammatory model. The expression IL-5R effects IL-5 analyzed human murine cells.Compound mice, compared single Akt1Myr exhibited increased tissue damage after repeat inductions inflammation, had accelerated development metastasis. M2 macrophages newly identified eosinophils co-localized fibrotic regions rather than infiltrating into tumors, consistent cell privilege. majority found pancreas lacked cytotoxic NKG2D marker. upregulated cells response then diminished advanced lesions. Although not previously described IL-5Rα during mouse progression expressed ductal adenocarcinomas (7 7 immunohistochemistry). stimulated migration activation through STAT5 signaling, thereby suggesting an unreported tumor-promoting for cancer.Chronic induces such as attracted areas fibrosis. Results suggest that compartment stimulates on increase motility. Collectively, IL-5/IL-5Rα signaling tumors novel mechanism facilitate progression. Additional file 1: Video Abstract.