Circulating microparticles in pancreatic cancer patients and their interactions with endothelial cells of engineered microvessel network
Authors: Li Xiang , Zhou Mi , Wong Joyce , He Pingnian 
Published: November 2023

Microparticles (MPs) are small plasma membrane‐derived vesicles released during cell activation and apoptosis and have been found to be elevated in the plasma of patients with cardiovascular diseases and cancers. However, the clear clinical significance of MPs in the pathogenesis of vascular complications and cancer progression remain to be identified. Pancreatic cancer is one of the most lethal cancers with the lowest survival rates. It characteristically creates an abnormal inflammatory or desmoplastic response, which may play a role in its resistance to systemic therapy and aggressive metastasis. MPs carry a range of antigens from their parental cells during activation and have been considered as biomarker for disease prognosis and mediator for inflammation. We hypothesize that the circulating MPs in pancreatic cancer patients are elevated and serve as vectors propagating inflammation in the vasculature. In this study, we characterized the profile of circulating MPs of pancreatic cancer patients and investigated their interactions with endothelial cells (ECs) in engineered microvessel network. The plasma MPs were analyzed with flow cytometry and the cell origins were identified with cell‐specific antibodies. The engineered microvessel network was generated by culturing primary human umbilical vein endothelial cells in microfluidic based microchannels with a continuous perfusion, which has shown well‐formed EC junctions with the capability for high resolution imaging. Our results showed that patients with pancreatic cancer (n=11) had elevated levels of MPs compared with healthy controls (n=8). About 90% of total plasma MPs were from platelets, leukocytes, and endothelial cells and over 50% of the MPs existed as aggregated units expressing multiple parental cell surface antigens. The effect of cancer patients’ plasma on ECs was investigated by direct perfusion of patients’ plasma into the cultured microvessel for 30 min under the physiological relevant shear flow. Then the engineered microvessels were perfused with FITC‐Annexin V, the phospholipid binding protein, to identify the adhered MPs on the vessel walls, as majority of the MPs have cell membrane phosphatidylserine exposed on their outer membrane. Confocal images revealed a significant number of adhered MPs on the ECs. No such effect was observed after the MPs were removed from the plasma. Our study demonstrated that pancreatic cancer patients have elevated circulating MPs that were mainly derived from blood cell origins, indicating an association between inflammation and pancreatic cancer. These MPs are highly adhesive and actively interact with ECs, which may further mediate leukocyte and tumor cell adhesion and migration. Our engineered microvessel network served as a perfect tool for the study of human plasma samples. Our findings also indicate that the circulating MPs have the potential to serve as a biomarker for pancreatic cancer prognosis and treatment outcomes.

Support or Funding Information

Supported by HL056237, HL084338 and DK097391.