Neutrophil Extracellular Traps and Pancreatic Cancer Development: A Vicious Cycle

SIMPLE SUMMARY: Cancer-associated thrombosis is a significant complication in cancer patients with various clinical consequences. Neutrophil extracellular traps (NETs), are associated with cancer development and hypercoagulability in various cancers, including pancreatic cancer. On the other hand, pancreatic cancer development is associated with increased NETs formation. This feedback mechanism suggests the existence of a vicious cycle between NETs and the tumor microenvironment in pancreatic cancer, that supports tumor development and may lead to cancer-associated thrombosis. ABSTRACT: Neutrophil extracellular traps (NETs) are a neutrophil-generated extracellular network of chromatin and chromatin-bound molecules with antimicrobial potency. Recent data suggest that NETs are associated with cancer progression and cancer-associated hypercoagulability. Pancreatic adenocarcinoma (PDAC) is a lethal type of cancer in which hypercoagulability and cancer-related thrombosis are among the main complications. In the current report, we summarize the available data on the interplay between NET formation and PDAC development. We conclude that NETs support a dual role during PDAC progression and metastasis. Their formation is on the one hand an important event that shapes the cancer microenvironment to support cancer cell proliferation, invasion and metastasis. On the other hand, NETs may lead to cancer-associated thrombosis. Both mechanisms seem to be dependent on distinct molecular mechanisms that link inflammation to cancer progression. Collectively, NET formation may contribute to the pathogenesis of PDAC, while during cancer development, the proinflammatory environment enables the induction of new NETs and thrombi, forming a vicious cycle. We suggest that targeting NET formation may be an effective mechanism to inhibit both PDAC development and the accompanying hypercoagulability.