Tumour-activated protein promotes cancer spread

Researchers at the University of California (UC), San Diego School of Medicine and San Diego Moores Cancer Center report that cancers physically alter cells in the lymphatic system – a network of vessels that transports and stores immune cells throughout the body – to promote the spread of disease, a process called metastasis. 

The findings have been published in this week's online edition of the Proceedings of the National Academy of Sciences.

Roughly 90 per cent of all cancer deaths are due to metastasis – the disease spreading from the original tumour site to multiple, distant tissues and finally overwhelming the patient's body. Lymph vessels are often the path of transmission, with circulating tumour cells lodging in the lymph nodes – organs distributed throughout the body that act as immune system garrisons and traps for pathogens and foreign particles.

The researchers, led by principal investigator Judith A. Varner, PhD, professor of medicine at UC San Diego Moores Cancer Center, found that a protein growth factor expressed by tumours, called VEGF-C, activates a receptor called integrin a4ß1 on lymphatic vessels in lymph node tissues, making them more attractive and sticky to metastatic tumour cells.

''One of the most significant features of this work is that it highlights the way that tumours can have long-range effects on other parts of the body, which can then impact tumour metastasis or growth,'' said Varner.

Varner said a4ß1 could prove to be a valuable biomarker for measuring cancer risk, since increased levels of the activated protein in lymph tissues is an indirect indicator that an undetected tumor may be nearby.

She said whole-body imaging scans of the lymphatic network might identify problem areas relatively quickly and effectively. ''The idea is that a radiolabeled or otherwise labeled anti-integrin a4ß1 antibody could be injected into the lymphatic circulation, and it would only bind to and highlight the lymphatic vessels that have been activated by the presence of a tumor.''

Varner noted that a4ß1 levels correlate with metastasis – the higher the level, the greater the chance of the cancer spreading. With additional research and clinical studies, doctors could refine treatment protocols so that patients at higher risk are treated appropriately, but patients at lower or no risk of metastasis are not over-treated.

The researchers noted in their studies that it is possible to suppress tumour metastasis by reducing growth factor levels or by blocking activation of the a4ß1 receptor.

Varner said an antibody to VEGF-R3 is currently in Phase 1 clinical trials. An approved humanized anti-a4ß1 antibody is currently approved for the treatment of multiple sclerosis and Crohn's disease. Varner said her lab at UC San Diego Moores Cancer Center is investigating the possibility of developing one for treating cancer.