Endothelial Protein C Receptor (EPCR), Protease Activated Receptor-1 (PAR-1) and Their Interplay in Cancer Growth and Metastatic Dissemination

Wojtukiewicz, Marek Z.; Hempel, Dominika; Sierko, Ewa; Tucker, Stephanie C.; Honn, Kenneth V.

doi:10.3390/cancers11010051

Cited by 25 publications

(20 citation statements)

References 110 publications

(166 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of abnormalities in blood coagulation in association with cancer have been demonstrated, including elevated fibrinogen, thrombin generation, enhanced expression of TF and cancer procoagulant [26]. An imbalance between activators and inhibitors of the hemostatic system is observed, which may contribute not only to increased prothrombotic tendency but also to tumor invasion, progression and metastasis [27][28][29][30][31][32]. A growing body of evidence indicates that different forms of anticancer treatment affect the hemostatic system in cancer patients [8,[33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Elevated Microparticles, Thrombin-antithrombin and VEGF Levels in Colorectal Cancer Patients Undergoing Chemotherapy

Wojtukiewicz

Mysliwiec

Sierko

et al. 2020

Pathol. Oncol. Res.

Self Cite

View full text Add to dashboard Cite

Hypercoagulable state and neoangiogenesis are common phenomena associated with malignancy. Cancer patients have increased levels of circulating endothelium-derived microparticles (EMPs), which have been hypothesized to be involved in numerous pathophysiological processes. Hemostasis and angiogenesis are also activated in colorectal cancer (CRC) patients. The study aimed to investigate potential influence of chemotherapy on EMPs, thrombin anti-thrombin complex (TAT) and vascular endothelial growth factor (VEGF) levels in CRC patients undergoing chemotherapy. The study group consisted of 18 CRC patients: 8 stage III colon cancer (CC) and 10 stage IV rectal cancer (RC) patients. EMPs, TAT and VEGF levels were assessed before chemotherapy and after the third course. Results were compared with 10 healthy subjects. EMP concentration was measured by flow cytometry, while TAT and VEGF concentrations were assayed employing ELISA. Compared to the control group, CC and RC patients had significantly higher levels of tissue factor (TF)-bearing and non-TF-bearing EMPs before and after three courses of chemotherapy. VEGF concentrations in CRC patients were higher than in the control groups and increased following chemotherapy. TAT levels were elevated in CRC patients before chemotherapy compared to healthy subjects and significantly increased after the third course of chemotherapy. No significant correlation was found either between EMP and TAT levels, or between EMP concentrations and VEGF levels in the study group. CRC patients have increased EMPs, and TAT as well as VEGF levels tend to increase during chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated Microparticles, Thrombin-antithrombin and VEGF Levels in Colorectal Cancer Patients Undergoing Chemotherapy

Wojtukiewicz

Mysliwiec

Sierko

et al. 2020

Pathol. Oncol. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although IBD patients are considered to be at high risk of developing colonic cancer, due to the effect of bacterial dysbiosis and chronic gut inflammation, the impact of PAR signaling in the onset and progression of intestinal cancer is less explored . Beyond being expressed in the healthy epithelium, PAR‐1 and PAR‐2 are highly expressed in human intestinal adenocarcinoma cell lines and in stromal cells, and could possibly enhance their proliferation and metastatic capacity .…”

Section: Involvement Of Pars In Gastrointestinal Tumor Progressionmentioning

confidence: 99%

Protease‐activated receptor signaling in intestinal permeability regulation

et al. 2019

View full text Add to dashboard Cite

Protease‐activated receptors (PARs) are a unique class of G‐protein‐coupled transmembrane receptors, which revolutionized the perception of proteases from degradative enzymes to context‐specific signaling factors. Although PARs are traditionally known to affect several vascular responses, recent investigations have started to pinpoint the functional role of PAR signaling in the gastrointestinal (GI) tract. This organ is exposed to the highest number of proteases, either from the gut lumen or from the mucosa. Luminal proteases include the host's digestive enzymes and the proteases released by the commensal microbiota, while mucosal proteases entail extravascular clotting factors and the enzymes released from resident and infiltrating immune cells. Active proteases and, in case of a disrupted gut barrier, even entire microorganisms are capable to translocate the intestinal epithelium, particularly under inflammatory conditions. Especially PAR‐1 and PAR‐2, expressed throughout the GI tract, impact gut permeability regulation, a major factor affecting intestinal physiology and metabolic inflammation. In addition, PARs are critically involved in the onset of inflammatory bowel diseases, irritable bowel syndrome, and tumor progression. Due to the number of proteases involved and the multiple cell types affected, selective regulation of intestinal PARs represents an interesting therapeutic strategy. The analysis of tissue/cell‐specific knockout animal models will be of crucial importance to unravel the intrinsic complexity of this signaling network. Here, we provide an overview on the implication of PARs in intestinal permeability regulation under physiologic and disease conditions.

show abstract

“…Reddel et al focus on the role played by thrombin in cancer–platelet cross-talk, with consequent increases in blood coagulation and cancer progression and metastasis [23]. Wojtukiewicz et al address the functional significance of Endothelial Protein C Receptor (EPCR), Protease-Activated Receptor-1 (PAR-1) and their interplay in cancer growth and metastatic spread [24]. Finally, Luu et al focus on bone marrow dysfunction and how this influences platelet function [25].…”

mentioning

confidence: 99%