Tie2 inhibition disrupts TMEM doorway function and reduces dissemination in pancreatic ductal adenocarcinoma - PubMed
a day ago
- #Pancreatic Cancer
- #Metastasis
- #Tie2 Inhibition
- TMEM doorways, composed of a tumor cell, a Tie2+ macrophage, and an endothelial cell, act as portals for intravasation in pancreatic ductal adenocarcinoma (PDAC).
- Tie2 inhibition disrupts TMEM doorway function, reducing vascular openings, transendothelial migration of tumor cells, and dissemination in PDAC models.
- Higher TMEM density in human PDAC correlates with aggressive pathology and decreases after neoadjuvant therapy.
- Rebastinib (Tie2 inhibitor) combined with FOLFIRINOX chemotherapy improves survival compared to FOLFIRINOX alone in PDAC therapeutic studies.
- Macrophage-specific Tie2 knockout confirms the role of Tie2 signaling in mediating PDAC dissemination through TMEM doorways.