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  • Arce, MaximilianoPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Adv Ctr Chron Dis ACCDiS, Santiago, Chile (author)

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

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-08-02
  • MDPI,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-394646
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-394646URI
  • https://doi.org/10.3390/cancers11081103DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

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  • Pinto, Mauricio P.Pontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile (author)
  • Galleguillos, MacarenaPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Munoz, CatalinaPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Lange, SoledadPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Ramirez, CarolinaPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Erices, RafaelaPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Univ Mayor, Vicerrectoria Invest, Santiago 7510041, Chile (author)
  • Gonzalez, PamelaPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Velasquez, EthelPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Comis Chilena Energia Nucl CCHEN, Santiago, Chile (author)
  • Tempio, FabianUniv Chile, Fac Med, Inst Biomed Sci, Santiago 8380453, Chile (author)
  • Lopez, Mercedes N.Univ Chile, Fac Med, Inst Biomed Sci, Santiago 8380453, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile (author)
  • Salazar-Onfray, FlavioUniv Chile, Fac Med, Inst Biomed Sci, Santiago 8380453, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile (author)
  • Cautivo, KellyPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Kalergis, Alexis M.Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile;Biomed Res Consortium Chile, Santiago 8331010, Chile (author)
  • Cruz, SebastianFdn Ciencia & Vida, Lab Immunoncol, Santiago, Chile (author)
  • Lladser, AlvaroMillennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile;Fdn Ciencia & Vida, Lab Immunoncol, Santiago, Chile (author)
  • Lobos-Gonzalez, LorenaAdv Ctr Chron Dis ACCDiS, Santiago, Chile;Fdn Ciencia & Vida, Lab Immunoncol, Santiago, Chile;Univ Desarrollo, Fac Med, Regenerat Med Ctr, Clin Alemana, Santiago 7650568, Chile (author)
  • Valenzuela, GuillermoPontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile (author)
  • Olivares, NixaPontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile (author)
  • Saez, ClaudiaPontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile (author)
  • Koning, TaniaUniv Austral Chile, Fac Med, Immunol Inst, Valdivia 5110566, Chile (author)
  • Sanchez, Fabiola A.Univ Austral Chile, Fac Med, Immunol Inst, Valdivia 5110566, Chile (author)
  • Fuenzalida, PatriciaPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile (author)
  • Godoy, AlejandroPontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Roswell Pk Comprehens Canc Ctr, Dept Urol, Buffalo, NY 14203 USA (author)
  • Contreras Orellana, PamelaAdv Ctr Chron Dis ACCDiS, Santiago, Chile;Univ Chile, Fac Med, Lab Cellular Commun, ICBM, Santiago 8380453, Chile (author)
  • Leyton, LisetteAdv Ctr Chron Dis ACCDiS, Santiago, Chile;Univ Chile, Fac Med, Lab Cellular Commun, ICBM, Santiago 8380453, Chile (author)
  • Lugano, RobertaUppsala universitet,Vaskulärbiologi(Swepub:uu)roblu911 (author)
  • Dimberg, AnnaUppsala universitet,Vaskulärbiologi(Swepub:uu)annadimb (author)
  • Quest, Andrew F. G.Adv Ctr Chron Dis ACCDiS, Santiago, Chile;Univ Chile, Fac Med, Lab Cellular Commun, ICBM, Santiago 8380453, Chile (author)
  • Owen, Gareth, IPontificia 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;Millennium Inst Immunol & Immunotherapy, Santiago 8331150, Chile (author)
  • Pontificia Univ Catolica Chile, Fac Biol Sci, Santiago 8331150, Chile;Adv Ctr Chron Dis ACCDiS, Santiago, ChilePontificia Univ Catolica Chile, Fac Med, Santiago 8331150, Chile (creator_code:org_t)

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