Common anti-coagulant suppresses growth and spread of tumours

New research suggests that the anti-coagulants known collectively as Low Molecular Weight Heparin (LMWH), routinely given to cancer patients to treat or lower the risk of thrombosis, may also suppress the growth and spread of tumours.

The research, led by Dr Camille Ettelaie of the University of Hull and Dr Anthony Maraveyas, consultant oncologist from Hull’s Castle Hill Hospital, has shown for the first time, that LMWH can lower the levels of tissue factor – a protein involved in clotting – being secreted by tumours.

Dr Ettelaie said: “Tissue factor’s role in healthy people is to promote blood clotting in wounds and aid repair. However, in cancer, we found that tumours secrete tissue factor as an inflammatory response to their interaction with growth factors in the blood, which they hijack to help them grow and spread.

High levels of tissue factor are known to cause thrombosis, which is one reason why cancer patients are particularly at risk of developing lethal deep vein blood clots.

“In addition, our previous research has shown that tumour cells which express high levels of tissue factor are more invasive, and other reports show that they metastasize rapidly and are resistant to therapy. Therefore, finding new ways to suppress the expression of tissue factor are crucial.”

Observational studies had shown that patients treated with LMWH to thin their blood also had reduced levels of tissue factor and several clinicians, including Dr Maraveyas, had noted that cancer patients treated with LMWH seem to have better clinical outcomes, such as survival; but until now, no-one knew why.

The team studied the effects of doses of LMWH, equivalent to those given therapeutically to cancer patients, on pancreatic cancer cells – an extremely aggressive cancer, characterised by high levels of tissue factor. This was followed by similar tests on four other cancer cell types - ovarian, breast, melanoma and colorectal. For each of the five cancer types, the team found that the LMWH interfered with the cancer cells’ interaction with growth factors, which in turn prevented tissue factor from being secreted.

Dr Maraveyas said: “To see this process suppressed in highly lethal cancer like pancreatic cancer and in a further four cancer types with high levels of tissue factor, raises the possibility of a universal treatment strategy that could benefit all cancer patients.”

The results showed that the suppression of tissue factor was a gradual process, which, Dr Maraveyas says supports a more protracted use of LMWH.

“What we have here is experimental evidence that a drug that is already known to be safe in humans as an anticoagulant may also suppress tumour growth directly and reduce resistance to treatment. I think this would also be a very useful way of lowering the risk of tumour regrowth in between chemotherapy and radiotherapy sessions.

The research is published online in the journal Biochimica et Biophysica Acta -Molecular Basis of Disease, and was part-funded by the Castle Hill Hospital Charity Fund.

Science News Source:University of Hull