Progesterone utilizes distinct membrane pools of tissue factor to increase coagulation and invasion and these effects are inhibited by TFPI

Soledad Henriquez, Claudia Calderon, Marisol Quezada, Bárbara Oliva, Maria Loreto Bravo, Evelyn Aranda, Sumie Kato, Mauricio A. Cuello, Jorge Gutiérrez, Andrew F.G. Quest, Gareth I. Owen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Tissue factor (TF) serving as the receptor for coagulation factor VII (FVII) initiates the extrinsic coagulation pathway. We previously demonstrated that progesterone increases TF, coagulation and invasion in breast cancer cell lines. Herein, we investigated if tissue factor pathway inhibitor (TFPI) could down-regulate progesterone-increased TF activity in these cells. Classically, TFPI redistributes TF-FVII-FX-TFPI in an inactive quaternary complex to membrane associated lipid raft regions. Herein, we demonstrate that TF increased by progesterone is localized to the heavy membrane fraction, despite progesterone-increased coagulation originating almost exclusively from lipid raft domains, where TF levels are extremely low. The progesterone increase in coagulation is not a rapid effect, but is progesterone receptor (PR) dependent and requires protein synthesis. Although a partial relocalization of TF occurs, TFPI does not require the redistribution to lipid rafts to inhibit coagulation or invasion. Inhibition by TFPI and anti-TF antibodies in lipid raft membrane fractions confirmed the dependence on TF for progesterone-mediated coagulation. Through the use of pathway inhibitors, we further demonstrate that the TF up-regulated by progesterone is not coupled to the progesterone increase in TF-mediated coagulation. However, the progesterone up-regulated TF protein may be involved in progesterone-mediated breast cancer cell invasion, which TFPI also inhibits.

Original languageEnglish (US)
Pages (from-to)3278-3285
Number of pages8
JournalJournal of Cellular Physiology
Volume226
Issue number12
DOIs
Publication statusPublished - Dec 1 2011

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ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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