Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation
Journal
Cancers
ISSN
2072-6694
Date Issued
2019
Author(s)
Maximiliano Arce
Mauricio P. Pinto
Macarena Galleguillos
Catalina Muñoz
Soledad Lange
Carolina Ramirez
Rafaela Erices
Pamela Gonzalez
Ethel Velasquez
Fabián Tempio
Mercedes N. Lopez
Flavio Salazar-Onfray
Kelly Cautivo
Alexis M. Kalergis
Sebastián Cruz
Álvaro Lladser
Guillermo Valenzuela
Nixa Olivares
Claudia Sáez
Tania Koning
Fabiola A. Sánchez
Patricia Fuenzalida
Alejandro Godoy
Pamela Contreras Orellana
Lisette Leyton
Roberta Lugano
Anna Dimberg
Andrew F.G. Quest
Gareth I. Owen
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Arce, M., Pinto, M. P., Galleguillos, M., Muñoz, C., Lange, S., Ramirez, C., Erices, R., Gonzalez, P., Velasquez, E., Tempio, F., Lopez, M. N., Salazar-Onfray, F., Cautivo, K., Kalergis, A. M., Cruz, S., Lladser, Á., Lobos-González, L., Valenzuela, G., Olivares, N., … Owen, G. I. (2019). Coagulation factor xa promotes solid tumor growth, experimental metastasis and endothelial cell activation. Cancers, 11(8), 1103. https://doi.org/10.3390/cancers11081103
Subjects
cancer
;
metastasis
;
melanoma
;
blood coagulation
;
vascular endothelium
;
inflammation