Circulating microparticles in pancreatic tumor patients and their roles in mediating leukocyte adhesion in intact microvessels
Authors: Zhou Mi , Xu Sulei , Feng Qilong , Wong Joyce , He Pingnian 
Published: November 2023

Pancreatic cancer is one of the nation's deadliest cancers with a dismal 6 percent five‐year survival rate. Pancreatic cancer characteristically creates an abnormal inflammatory or desmoplastic response, which may play a role in its resistance to systemic therapy and aggressive metastasis. Recent studies in circulating microparticles (MPs), the small plasma membrane‐derived vesicles (0.1–1um) released during cell activation, indicated that elevated MPs occur in many cardiovascular diseases, as well as in cancer patients. Since the released MPs carry a range of antigens depending on the type and activation state of their parental cells, they have been considered as biomarker to indicate the disease status and predict the prognosis. The objectives of our study are to investigate the relationship between pancreatic cancer and vascular inflammation and evaluate whether circulating MPs can be a potential biomarker for pancreatic cancer prognosis and treatment outcomes. In this study we characterized the profile of circulating MPs in patients with malignant and non‐malignant pancreatic diseases, investigated the interaction of cultured pancreatic cancer cell‐derived MPs (PACMPs) with blood and endothelial cell‐derived MPs, and explored the roles of PACMPs in mediating vascular inflammation. Flow cytometry was used to quantify plasma MPs, and identify MP cell origins using antibodies directly against cell specific antigens. Compared with healthy controls (n=8), patients with pancreatic cancer (n=11) and pancreatic cyst (nonmalignant, n=7) all had elevated levels of MPs. About 90% of total plasma MPs were from platelets, leukocytes, and endothelial cells. Over 50% of the MPs existed as aggregated units expressing multiple parental cell surface antigens. Electron microscopy and atomic force microscopy delineated the aggregation profiles of plasma MPs. When PACMPs were introduced into cancer patients’ plasma, more than 50% of the plasma MPs bound with PACMPs, and 32% of the plasma MPs that bound with PACMPs express platelet specific antigen. The interaction between PACMPs and vascular endothelial cells were investigated in individually perfused rat venules. After perfusing vessels with PACMPs followed by annexin V staining, confocal images show a significant number of adhered PATMPs in the microvessel walls. After resuming blood flow in PACMP perfused vessels, leukocyte adhesion was significantly increased from 3 ± 1 (control) to 13 ± 3 per 100 um of vessel length. Our results showed that both patients with malignant and non‐malignant pancreatic diseases had elevated circulating MPs, indicating an association between pancreatic diseases and inflammation. The increased plasma MPs, mainly from blood cells and ECs origins, and PACMPS are highly adhesive. They not only interact with each other, but also interact with normal ECs and mediate leukocyte adhesion, which may play important roles in propagation of the inflammation and contribute to pancreatic cancer progression and metastasis.

Support or Funding Information

Supported by HL056237, HL084338 and DK097391.