Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Aberrant tumor pericytes in pancreatic ductal adenocarcinoma: a barrier and opportunity for therapeutic advances

There is a lack of effective treatment for PDAC, often due to abnormal and leaky blood vessels and a lack of proper pericyte coverage, contributing to the inability of the drugs to reach the tumor. However, in PDAC, the pericyte (PC)-endothelial (EC) cell communication is decreased or non-existent, thereby affecting drug delivery and immune function. We propose to re-program tumor-associated pericytes to normalize the tumor blood vessels and revert them to an optimal functional state. We previously showed that tumor-associated pericytes in PDAC exhibit ectopic αSMA expression up to ten times higher than normal pericytes, correlating strongly with vascular instability and hypoxia. Due to significant involvement of αSMA in cellular morphology and structure, tumor-associated pericytes presented biomechanical abnormalities. We employed scRNA sequencing to define the pathological signature of tumor-associated pericytes and identify therapeutic targets for vascular normalization. We identified a distinct pericyte subpopulation characterized by elevated expression of αSMA, MCT1, and gap junction proteins. Alterations in basement membrane gene expression and smooth muscle markers further emphasized the disrupted vascular architecture and impaired pericyte-endothelial cell adhesion within the tumor microenvironment. Our data reveals consistently upregulated monocarboxylate transporters in vascular cells.. We have shown that in PDAC, MCT1 lactate exporters are upregulated in EC and PCs. The high amount of lactate produced by PCs decreases the pH in the basement membrane. So, we knocked down MCT1 transporters in PCs to increase basement pH, leading to improved PC-EC attachment and pericyte homeostasis.