Investigating the Role of Piezo1 in Pancreatic Cancer-Related Immune Suppression and Disease Progression
Abstract
Tumor stiffness and peri-tumoral fibrosis have emerged as factors limiting therapy for pancreatic ductal adenocarcinoma (PDA). Novel drugs directly targeting tumor stiffness have shown efficacy in preclinical studies and early clinical trials in pancreatic cancer. Piezo1 is a recently-discovered mechano-sensitive ion channel that governs organogenesis in response to physical pressure. Since PDA is subject to the physical pressures associated with progressive fibrosis, we postulated a role for Piezo1 in regulating disease progression. We found marked upregulation of Piezo1 in PDA. We also found that blocking Piezo1 signaling in vivo in PDA is protective and activates T cells and redirects myeloid cellular differentiation away from immune-suppressive subsets and protects against PDA. By contrast, activating Piezo1 promotes PDA growth and the accumulation of immune-suppressive monocytic cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1092705
Entities
People
- George Miller
Organizations
- Grossman School of Medicine