Researchers have discovered how secondary cancers in the lung, called lung metastases, can take over healthy blood vessels in order to fuel their growth.
The new study, conducted in mice and rats, showed that tumours can grow around and make use of existing blood vessels in the lung – using a process called vessel co-option – rather than relying exclusively on stimulating the formation of new vessels that then ‘sprout’ into the tumour.
It well known that tumours contain blood vessels, and access to these blood vessels is key to the growth of tumours, because it supplies them with oxygen and nutrients. Previously it was assumed that tumours rely on stimulating the formation of new vessels – a process which is called angiogenesis.
Scientists from The Institute of Cancer Research, London, working in collaboration with others in Vienna and Budapest, showed that vessel co-option occurs in lung metastases of diverse tumour types, including breast cancer, colorectal cancer, melanoma and fibrosarcoma. Importantly, they showed that the process of vessel co-option is highly co-ordinated.
The study, published in the Journal of Pathology, found that vessel co-option occurs in two stages. During the early steps of vessel co-option, tumours invade around the healthy walls of alveoli – small chambers which make up the bulk of the lung – and incorporate both the blood vessels and the cells that line the alveoli, which are called pneumocytes. Then, once the cancerous cells have seized these healthy blood vessels, they strip away the pneumocytes.
In the study, the researchers looked in six different models of lung metastasis. In five of the models, the pneumocytes were broken into fragments but the co-opted vessels survived, and the co-opted blood vessels then enabled the tumours to grow. Remarkably, the scientists found little evidence for the presence of sprouting angiogenesis in the lung tumours they studied.
The study was supported by a range of international research funders, including Breakthrough Breast Cancer and NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR in the UK.
Dr Andrew Reynolds, Leader of the Tumour Biology Team at the ICR, said: "Our study reinforces the idea that tumours can grow perfectly well by just recruiting the vessels found in nearby healthy tissue and that they do not need to stimulate the growth of new vessels. This is not only fascinating, but it could be very important clinically.
“Many drugs have been designed to target sprouting angiogenesis, but they are not as effective in people with cancer as we would like. We now need to understand whether vessel co-option is a mechanism that explains why some tumours do not respond to these anti-angiogenic drugs.
“Moreover, by understanding the molecular mechanisms of vessel co-option better, we should be able to design new therapies that can effectively target the tumours that use vessel co-option. These therapies could be used in patients whose tumours have spread, or metastasised, to other parts of the body – a stage of the disease which is typically hard to treat."