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Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation
Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Adv Ctr Chron Dis ACCDiS, Santiago, Chile.
Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile.ORCID iD: 0000-0003-2484-8033
Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile.
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 8, article id 1103Article in journal (Refereed) Published
Abstract [en]

Hypercoagulable state is linked to cancer progression; however, the precise role of the coagulation cascade is poorly described. Herein, we examined the contribution of a hypercoagulative state through the administration of intravenous Coagulation Factor Xa (FXa), on the growth of solid human tumors and the experimental metastasis of the B16F10 melanoma in mouse models. FXa increased solid tumor volume and lung, liver, kidney and lymph node metastasis of tail-vein injected B16F10 cells. Concentrating on the metastasis model, upon coadministration of the anticoagulant Dalteparin, lung metastasis was significantly reduced, and no metastasis was observed in other organs. FXa did not directly alter proliferation, migration or invasion of cancer cells in vitro. Alternatively, FXa upon endothelial cells promoted cytoskeleton contraction, disrupted membrane VE-Cadherin pattern, heightened endothelial-hyperpermeability, increased inflammatory adhesion molecules and enhanced B16F10 adhesion under flow conditions. Microarray analysis of endothelial cells treated with FXa demonstrated elevated expression of inflammatory transcripts. Accordingly, FXa treatment increased immune cell infiltration in mouse lungs, an effect reduced by dalteparin. Taken together, our results suggest that FXa increases B16F10 metastasis via endothelial cell activation and enhanced cancer cell-endothelium adhesion advocating that the coagulation system is not merely a bystander in the process of cancer metastasis.

Place, publisher, year, edition, pages
MDPI, 2019. Vol. 11, no 8, article id 1103
Keywords [en]
cancer, metastasis, melanoma, blood coagulation, vascular endothelium, inflammation
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-394646DOI: 10.3390/cancers11081103ISI: 000484438000063PubMedID: 31382462OAI: oai:DiVA.org:uu-394646DiVA, id: diva2:1362010
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Swedish Cancer Society, CAN 2017/502Available from: 2019-10-17 Created: 2019-10-17 Last updated: 2019-10-17Bibliographically approved

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