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Distinct cell populations differentially regulate cancer-associated thrombosis

last modified Jan 11, 2016 11:37 AM

Cancer patients commonly suffer from thrombosis and thrombotic complications including pulmonary embolism. Researchers in the Department of Physiology, Development and Neuroscience have recently shown that hypoxia-inducible factor 1 (HIF1) in different cell types can regulate cancer-induced hypercoagulation. HIF1 is activated by reductions in oxygen levels (i.e. hypoxia) and this transcription factor subsequently controls the vascular response to hypoxia. HIF1 was isolated more than 20 years ago by Prof Gregg Semenza and colleagues (Johns Hopkins, USA); this “master regulator” has since been established as a factor that stimulates wide-ranging vascular changes during malignancy, including but not limited to new blood vessel formation (angiogenesis).

In a recent study published in Blood, Dr Colin Evans, Prof Randall Johnson and others have shown that HIF1 can also modulate the likelihood of thrombus formation following the onset of cancer. These investigations of the impact of cell-specific HIF1 on plasma clotting and pulmonary thrombosis revealed that the pro-coagulant impact of HIF1 in tumor cells could be opposed by HIF1 in endothelial cells. Collaborative studies with a clinical oncology group led by Prof Mattias Belting (Lund University, Sweden) also demonstrated that HIF1 levels in human breast tumors are positively correlated with levels of active tissue factor (i.e. the initiator of the coagulation cascade).

Together these findings highlight the importance of considering potential side effects of systemic HIF therapies when managing thrombotic complications in cancer patients. They also identify cell-specific HIF1 as a potential therapeutic target for therapies that aim to regulate coagulation. A better understanding of mechanisms that control cancer-associated thrombosis could lead to the development of novel treatments for patients such as those with malignant hypercoagulopathy (Trousseau’s Syndrome).

Studies were funded by a Wellcome Trust Principal Research Fellowship to Prof Johnson and by pump-priming grants from the British Society for Haematology and the BHF Cambridge Centre of Excellence to Dr Evans. Further studies from the same group continue to elucidate the effects of cell-specific HIFs in other pulmonary and cardiovascular disorders including hypertension, inflammation, and sepsis.

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