Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation

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dc.contributor.authorArce, Maximiliano
dc.contributor.authorPinto, Mauricio P.
dc.contributor.authorGalleguillos, Macarena
dc.contributor.authorMuñoz, Catalina
dc.contributor.authorLange, Soledad
dc.contributor.authorRamírez, Carolina
dc.contributor.authorErices, Rafaela
dc.contributor.authorGonzález, Pamela
dc.contributor.authorVelasquez, Ethel
dc.contributor.authorTempio, Fabián
dc.contributor.authorLópez, Mercedes N.
dc.contributor.authorSalazar-Onfray, Flavio
dc.contributor.authorCautivo, Kelly
dc.contributor.authorKalergis, Alexis M.
dc.contributor.authorCruz, Sebastián
dc.contributor.authorLladser, Álvaro
dc.contributor.authorLobos-González, Lorena
dc.contributor.authorValenzuela, Guillermo
dc.contributor.authorOlivares, Nixa
dc.contributor.authorSáez, Claudia
dc.contributor.authorKoning, Tania
dc.contributor.authorSánchez, Fabiola A.
dc.contributor.authorFuenzalida, Patricia
dc.contributor.authorGodoy, Alejandro
dc.contributor.authorContreras Orellana, Pamela
dc.contributor.authorLeyton, Lisette
dc.contributor.authorLugano, Roberta
dc.contributor.authorDimberg, Anna
dc.contributor.authorQuest, A.F.G.
dc.contributor.authorOwen, Gareth I.
dc.date.accessioned2019-11-26T21:06:28Z
dc.date.available2019-11-26T21:06:28Z
dc.date.issued2019
dc.description.abstractHypercoagulable 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.
dc.format.extent21 p.
dc.identifier.citationCancers, 2019, 11, 1103
dc.identifier.urihttp://hdl.handle.net/11447/2867
dc.language.isoen
dc.subjectCáncer
dc.subjectMetastasis
dc.subjectMelanoma
dc.subjectBlood coagulation
dc.subjectVascular endothelium
dc.subjectInflammation
dc.titleCoagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation

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