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Anthracycline treatment of the human monocytic leukemia cell line THP-1 increases phosphatidylserine exposure and tissue factor activity.

Abstract：

INTRODUCTION:Cancer associated thrombosis is a well-recognized phenomenon that results in considerable patient morbidity and mortality. Malignancy conveys an increased risk for thrombosis and chemotherapy further elevates this risk. The pathophysiological mechanisms underlying this process remain poorly defined. MATERIALS AND METHODS:A human acute monocytic leukemia cell line (THP-1) was treated with commonly used anthracycline chemotherapeutics at concentrations similar to those found in the plasma of cancer patients. Cells were analyzed for tissue factor (TF) mRNA, protein, and activity. Microparticle (MP) TF activity was also measured. Phosphatidylserine (PS) exposure on cells and MPs was analyzed by flow cytometry. PS levels on MPs was also evaluated in an annexin V capture assay. RESULTS:Anthracycline treatment of THP-1 cells resulted in a concentration-dependent increase in cellular TF activity without a change in TF protein, which was associated with increased PS exposure on the cell surface and apoptosis. The increase in TF activity was abolished by annexin V or lactadherin indicating that PS exposure was required. Anthracycline treatment of THP-1 cells also increased the number of TF-positive MPs. CONCLUSION:Treatment of THP-1 cells with anthracyclines induces apoptosis and increases cellular TF activity. The increased activity required an increase in exposure of PS. Additionally, anthracyclines increase the release of TF-positive MPs from THP-1 cells. We propose that the increase in cellular TF activity in circulating leukemic cells, combined with increased numbers of TF-positive MPs, may contribute to thrombosis in cancer patients receiving chemotherapy.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Boles JC,Williams JC,Hollingsworth RM,Wang JG,Glover SL,Owens AP 3rd,Barcel DA,Kasthuri RS,Key NS,Mackman N

doi

10.1016/j.thromres.2011.06.022

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

197-203

issue

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(11)00336-7

journal_volume

129

pub_type

杂志文章

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Anthracycline treatment of the human monocytic leukemia cell line THP-1 increases phosphatidylserine exposure and tissue factor activity.