Structural and molecular insight into antibody recognition of dynamic neoepitopes in membrane tethered MUC1 of pancreatic cancer cells and secreted exosomes.

ABSTRACT: Pancreatic cancer is highly metastatic and has poor prognosis, mainly due to delayed detection, often after metastasis has occurred. A novel method to enable early detection and disease intervention is strongly needed. Here we unveil for the first time that pancreatic cancer cells (PANC-1) and secreted exosomes express MUC1 bearing cancer-relevant dynamic epitopes recognized specifically by an anti-MUC1 antibody (SN-131), which binds specifically core 1 but not core 2 type O-glycans found in normal cells. Comprehensive assessment of the essential epitope for SN-131 indicates that PANC-1 cells produce dominantly MUC1 with aberrant O-glycoforms such as Tn, T, and sialyl T (ST) antigens. Importantly, SN-131 showed the highest affinity with MUC1 bearing ST antigen at the immunodo

SUBMITTER: Wakui H 

PROVIDER: S-EPMC10398351 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature