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Ganglioside-Mediated Neural-Acinar Crosstalk Facilitates Pancreatic Carcinogenesis via Metaplastic Niche Remodeling - PubMed

3 hours ago
  • #Pancreatic Cancer
  • #Gangliosides
  • #Neural Crosstalk
  • Neural networks are a crucial but underexplored part of the pancreatic tumor microenvironment.
  • Acinar-to-ductal metaplasia (ADM) and neural remodeling interact reciprocally during pancreatic ductal adenocarcinoma (PDAC) initiation and progression.
  • Inflammation and Kras mutation induce ADM in the pancreas.
  • Metaplastic epithelial cells promote neuritogenesis, while neural remodeling affects ADM formation.
  • Ganglioside metabolites, particularly GM3, mediate bidirectional crosstalk between neural and epithelial cells.
  • B4GALT5 is overexpressed in ADM, PanIN, and PDAC lesions and plays a key role in disease progression.
  • Pharmacological inhibition of B4GALT5 reduces neuronal growth and reverses ADM formation and progression.
  • Neuronal-ADM interactions and glycosphingolipid metabolism are potential therapeutic targets for early PDAC intervention.