Crosstalk between cancer and haemostasis

F. Langer; C. Bokemeyer

doi:10.5482/ha-1160

Hämostaseologie, Table of Contents

Hamostaseologie 2012; 32(02): 95-104
DOI: 10.5482/ha-1160

Review

Schattauer GmbH

Crosstalk between cancer and haemostasis

Implications for cancer biology and cancer-associated thrombosis with focus on tissue factorZusammenspiel von Tumorwachstum und HämostaseaktivierungBedeutung von Tissue- Faktor für Tumorbiologie und tumorassoziierte Thrombose

F. Langer

¹Hubertus Wald Tumorzentrum – Universitäres Cancer Center Hamburg, Universitätsklinikum Hamburg-Eppendorf

,

C. Bokemeyer

¹Hubertus Wald Tumorzentrum – Universitäres Cancer Center Hamburg, Universitätsklinikum Hamburg-Eppendorf

› Author Affiliations

Abstract

Summary

Cancer is characterized by bidirectional interrelations between tumour progression, coagulation activation, and inflammation. Tissue factor (TF), the principal initiator of the coagulation protease cascade, is centrally positioned in this complex triangular network due to its pleiotropic effects in haemostasis, angiogenesis, and haematogenous metastasis. While formation of macroscopic thrombi is the correlate of cancer-associated venous thromboembolism (VTE), a major healthcare burden in clinical haematology and oncology, microvascular thrombosis appears to be critically important to blood-borne tumour cell dissemination. In this regard, expression of TF in malignant tissues as well as shedding of TFbearing microparticles into the circulation are thought to be regulated by defined genetic events relevant to pathological cancer progression, thus directly linking Trousseau’s syndrome to molecular tumourigenesis.

Because pharmacological inhibition of the TF pathway in selective tumour types and patient subgroups would be in line with the modern concept of individualized, targeted anti-cancer therapy, this review will focus on the role of TF in tumour biology and cancer-associated VTE.

Zusammenfassung

Krebserkrankungen sind durch wechselseitige Beziehungen zwischen Tumorprogression, Hämostaseaktivierung und Entzündungsreaktion gekennzeichnet. Tissue-Faktor (TF), der wichtigste Initiator der Gerinnungskaskade, nimmt eine zentrale Position in diesem Netzwerk ein, da er vielseitige Funktionen in der Hämostase, Angiogenese und hämatogenen Metastasierung ausübt. Während der tumorassoziierten venösen Thromboembolie (VTE) die Ausbildung makroskopischer Thromben zugrunde liegt, scheint die mikrovaskuläre Thrombose für die hämatogene Tumorzellaussaat von Bedeutung zu sein. Vor diesem Hintergrund wird angenommen, dass sowohl die TF-Expression in malignen Geweben als auch die Freisetzung von TF-positiven Mikro- partikeln in das Blut durch definierte, für die Tumorentstehung relevante Mutationen reguliert werden. Hierdurch wird das Trousseau- Syndrom direkt mit der Krankheitsprogression in Verbindung gebracht.

Da eine pharmakologische TF-Hemmung in selektierten Patientensubgruppen dem modernen Konzept einer individualisierten, zielgerichteten Krebstherapie gerecht würde, befasst sich diese Arbeit mit der Rolle von TF in der Tumorbiologie und der tumorassoziierten VTE.

Keywords

Cancer - thrombosis - tissue factor - micro- particles

Schlüsselwörter

Tumor - Thrombose - Tissue-Faktor - Mikropartikel

Full Text

References

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