Thromb Haemost 2007; 98(02): 283-286
DOI: 10.1160/TH07-03-0163
Theme Issue Article
Schattauer GmbH

Microfluidic reveals generation of platelet-strings on tumoractivated endothelium

Tobias Goerge*
1   University of Münster, Department of Dermatology, Münster, Germany
2   CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
,
Felix Kleinerüschkamp
1   University of Münster, Department of Dermatology, Münster, Germany
,
Alexej Barg
1   University of Münster, Department of Dermatology, Münster, Germany
,
Eva-Maria Schnaeker
1   University of Münster, Department of Dermatology, Münster, Germany
,
Volker Huck
1   University of Münster, Department of Dermatology, Münster, Germany
,
Matthias F. Schneider
3   University of Augsburg, Department of Biophysics, Augsburg, Germany
,
Martin Steinhoff
1   University of Münster, Department of Dermatology, Münster, Germany
,
Stefan W. Schneider
1   University of Münster, Department of Dermatology, Münster, Germany
› Author Affiliations
Further Information

Publication History

Received 01 March 2007

Accepted after revision 14 May 2007

Publication Date:
28 November 2017 (online)

Summary

Neoplastic diseases are often associated with thromboembolic events,however the precise mechanism underlying this observation is a matter of ongoing investigation. It is known that matrixmetalloproteinase- 1 (MMP-1) canonically activates the thrombin receptor (PAR-1) and we recently reported that highly metastatic tumor cells of melanoma and colon cancer are secreting matrixmetalloproteinase-1. This tumor-derived MMP1 was shown to be a major activator of endothelial PAR-1, thus leading to endothelial cell activation. As tumor-induced thrombosis is a characteristic of metastazing tumors, we investigated whether tumor-derived supernatant (TUSN) from melanoma and colon cancer may induce adhesion of circulating platelets,an initial step in thrombus formation.A time-course study revealed that TU-SN induces a rapid secretion of von Willebrand factor (VWF) within minutes. Using a novel microfluidic device we analyzed platelet-endothelial interactions in a closed circuit. Immunofluorescence imaging showed that TU-SN rapidly induces platelet- string formation via secreted VWF. We demonstrated that tumor-derived supernatant is a potent agonist inducing platelet adhesion under flow conditions.

* Current address for TG.


 
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