Journal
BRITISH JOURNAL OF CANCER
Volume 115, Issue 3, Pages 332-338Publisher
SPRINGERNATURE
DOI: 10.1038/bjc.2016.170
Keywords
macrophage; microparticles; mucins; pancreatic cancer; survival; thrombosis; tissue factor
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Funding
- Dutch Cancer Society [KWF UL 2006-3618]
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Background: Cancer-related venous thromboembolism (VTE) heralds a poor prognosis, especially in pancreatic adenocarcinoma (PAC). Tissue factor (TF) is implicated as one of the main culprits in PAC-associated VTE and disease progression. Methods: In a prospective cohort study of 79 PAC patients, we measured plasma CA19-9 and microparticle-associated TF activity (MP-TF activity). In addition, we enumerated TF(+)MPs and MUC1(+)MPs in plasma (n = 55), and studied the expression of TF, MUC1, CD31 and CD68 in tumour tissue (n = 44). Results: Plasma MP-TF activity was markedly elevated in PAC patients with VTE compared with those without (median: 1925 vs 113 fM Xa min(-1); P<0.001) and correlated with the extent of thromboembolic events, metastatic disease and short survival. Similar results were found for CA19-9. Patients with massively progressing thrombosis and cerebral embolisms despite anticoagulant therapy (n = 3) had the highest MP-TF activities (12 118-40 188 fM Xa min(-1)) and CA19-9 (40 730-197 000 kU l(-1)). All tumours expressed MUC1 and TF. MP-TF activity did not correlate with intensity of TF expression in adenocarcinoma cells, but corresponded with numbers of TF+ macrophages in the surrounding stroma. Conclusions: Circulating TF(+)MPs and mucins may concertedly aggravate coagulopathy in PAC. Understanding of underlying mechanisms may result in new treatment strategies for VTE prevention and improvement of survival.
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