Jagged 1 restrains malignant progression in pancreatic neuroendocrine neoplasia

#3463

Introduction: Notch pathway is a pivotal regulator of pancreatic organogenesis and postnatal maintenance, yet its role in pancreatic neuroendocrine neoplasias (pNENs) remains ill-defined.

Aim(s): To characterize Notch in pNENs by means of tumor tissue profiling (Notch receptors, ligands and downstream effectors) and ad-hoc validation of selected pathway components in in vitro and in vivo models.

Materials and methods: Archival pNENs (FFPE surgical samples; n#18, mostly G1–G2 WHO2019) were subjected to IHC and targeted transcriptomics analyses (RT-PCR on FFPE-derived mRNA). Notch axis components were mapped against clinical variables and conventional pathology indices. Selected targets were further explored in vitro, utilizing wild-type BON1 cell line and the derived strains with altered expression of Notch ligands. The role of Jag1 signaling in BON1 cells was also evaluated in a murine xenotransplantation model.

Conference:

Presenting Author:

Authors: Paramonov V, Mamaeva V, Laiho I, Kronqvist P, Vázquez-Ulloa E,

Keywords: pancreatic neuroendocrine tumor/neoplasia, Notch pathway, Jagged 1,