Thrombomodulin: tumour biology and prognostic implications.
BACKGROUND
Thrombomodulin (TM) is an endothelial receptor that exerts anti-coagulant, anti-fibrinolytic, and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. There is growing evidence that TM plays a role in tumour behaviour.


METHODS
The electronic literature (1966-2004) was reviewed with a specific focus on tumour biology.


RESULTS
TM is expressed on both the endothelium and tumour cells in several cancers. Loss of expression denotes a more malignant profile with poorer prognosis. Loss of TM is mediated by hypoxia, endotoxin, and various cytokines, while up-regulation can be achieved by pharmacological manipulation (e.g. pentoxyfylline and statins).


CONCLUSIONS
Originally described as an endothelial anticoagulant, TM plays a key role in tumour biology and prognostics, and provides a potential therapeutic target in impeding cancer spread.
Hanly
A M
AM
Department of Surgery, Research and Education Building, Beaumont Hospital, Beaumont, Dublin 9, Ireland. amhanly@indigo.ie
Hayanga
A
A
Winter
D C
DC
Bouchier-Hayes
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011237:Predictive Value of Tests; D011379:Prognosis; D018180:Thrombomodulin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D018180:Thrombomodulin; D010431:Pentoxifylline