# mechanism of venous thrombosis in pancreatic cancer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $554,371

## Abstract

Venous thromboembolism (VTE) is increased in cancer patients and is commonly referred to as cancer-
associated thrombosis (CAT). Rates of VTE vary among different cancer types with pancreatic cancer having
one of the highest rates of CAT (12-42%). This suggests that there are cancer type-specific mechanisms of
VTE. We and others have used mouse models to investigate mechanisms of CAT in different types of cancer.
Our previous studies have shown that tumor-derived tissue factor (TF) increases thrombus size in mice
bearing human pancreatic tumors in a new model of CAT. We will build on this observation by determining the
role of the intrinsic coagulation pathway, neutrophils/neutrophil extracellular traps (NETs) and tumor-derived
and host-derived plasminogen activator inhibitor type-1 (PAI-1) in venous thrombosis in tumor-bearing mice.
We have found that mice bearing human and murine pancreatic tumors have increased levels of circulating
FIXa-antithrombin (AT) complexes (indicating activation of the intrinsic coagulation cascade), neutrophils,
plasma citrullinated histone H3 (H3Cit) (indicating increased NET formation), and increased levels of PAI-1
(indicating a hypofibrinolytic state). In this proposal. we will use xenograft and allograft mouse models as well
as multiple human and murine pancreatic cancer cell lines and patients derived xenografts. We will use genetic
and pharmacologic approaches to comprehensively determine the roles of the intrinsic coagulation pathway,
neutrophils, NETs and PAI-1 in pancreatic CAT. Targeting the intrinsic pathway, neutrophils/NETs and PAI-1
may reduce VTE in pancreatic cancer patients with less risk of bleeding.

## Key facts

- **NIH application ID:** 9928103
- **Project number:** 5R01HL147149-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nigel Mackman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $554,371
- **Award type:** 5
- **Project period:** 2019-05-15 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928103

## Citation

> US National Institutes of Health, RePORTER application 9928103, mechanism of venous thrombosis in pancreatic cancer (5R01HL147149-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928103. Licensed CC0.

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