'Gatekeeper' cells could prevent cancer spread
Wednesday 18 January 2012
Laboratory research in the US has discovered that a little-studied 'gatekeeper' cell may prevent cancer spreading around the body.
Crucially, the study suggested that certain cancer drugs might destroy these cells and increase the chances of a tumour spreading.
But a Cancer Research UK scientist said that this these adverse effects have not been observed in patients, only in tissue samples.
The scientists from Harvard Medical School, publishing in the journal Cancer Cell, studied cells called pericytes, which coat blood vessels and support their growth.
The researchers removed pericytes from breast tumours in mice. The size of tumours decreased by 30 per cent over 25 days, but there was also a three-fold increase in the number of tumours that had spread to the animals's lungs.
Lead researcher Professor Raghu Kalluri, said: "If you just looked at tumour growth, the results were good. But when you looked at the whole picture, inhibiting tumour vessels was not controlling cancer progression. The cancer was, in fact, spreading."
A closer look revealed an increase in oxygen-starved - hypoxic - areas in tumours that lacked pericytes.
Prof Kalluri suggested that cancer cells use genetic survival tactics to respond to a lack of oxygen, becoming more mobile and moving through leaky blood vessel walls.
The researchers then carried out experiments with imatinib (Glivec) and sunitinib (Sutent). Both can cut off new blood vessel growth - angiogenesis - in some cancers. And both are also known to decrease the number of pericytes in tumours.
Tests on mice showed that both drugs reduced pericyte numbers by 70 per cent, while the rate of cancer spread tripled.
To test whether their findings might be relevant to patients, the scientists examined 130 human breast cancer samples. Those with the lowest numbers of pericytes were most likely to have come from aggressive cancers that had spread.
But experts from Cancer Research UK said it was too early to say whether the laboratory findings were applicable to patients.
Professor Kairbaan Hodivala-Dilke, a Cancer Research UK expert on angiogenesis, said: "This important work builds on what we already know about these drugs - that they can be very effective at shrinking tumours, but that we need to carefully monitor how they affect cancer spread.
"All the evidence about metastasis so far - including this latest research - has been from experiments in the lab, and the effects on cancer spread haven't been reported in patients who are being treated with anti-angiogenic drugs."
"But work like this to understand the complexity of a tumour's response to treatment is vital to help us pre-empt any unwanted effects in the clinic."
Dr Joanna Owens, Cancer Research UK's science information manager also moved to reassure patients.
"Drugs that block blood vessel formation - so called anti-angiogenic therapies - are a relatively new type of treatment with enormous promise for treating cancer. These types of drugs are only used after extensive trials that demonstrate a clear benefit for some patients," she said.
"Cancer is a complex disease and we need research like this to help us learn how to tackle it more effectively," she added.
Copyright Press Association 2012
- Cooke, V., LeBleu, V., Keskin, D., Khan, Z., O'Connell, J., Teng, Y., Duncan, M., Xie, L., Maeda, G., Vong, S., Sugimoto, H., Rocha, R., Damascena, A., Brentani, R., & Kalluri, R. (2012). Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway Cancer Cell, 21 (1), 66-81 DOI: 10.1016/j.ccr.2011.11.024
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