Research led by Barts Cancer Institute (BCI), Queen Mary University of London, has identified a novel mechanism that controls tumour growth, involving a particular protein expressed by specialised cells within tumour blood vessels. The study highlights new pathways that may represent targets for the development of cancer treatments.
The formation of new blood vessels in a process known as angiogenesis is an essential part of cancer progression. Blood vessels deliver nutrients and oxygen to tumours, which are required for tumour growth and spread. Blood vessels are made up of two main layers: An internal layer of fragile endothelial cells and an outer layer of structural cells called pericytes. Historically, pericytes have mainly been shown to control endothelial cell proliferation, differentiation and maintain blood vessel stability; however more recently, research is beginning to shed light on the interactions between pericytes and tumour cells.
This study, published today in Nature Communications and funded by Cancer Research UK, focused on a particular protein within pericytes called focal adhesion kinase (FAK). Led by BCI’s Dr Louise Reynolds and Professor Kairbaan Hodivala-Dilke, the researchers found that when they deleted this protein from pericytes in preclinical models of melanoma, lung cancer and pancreatic cancer, tumour progression was enhanced.
Joint first author of the study, Dr Reynolds said:
“Our study uncovers a previously unrecognised role for pericyte FAK. We found that this protein plays an important role in controlling tumour angiogenesis and thus tumour growth, through controlling the release of pericyte-derived signals that cross-talk with tumour cells.”
On further investigation, the team found that when FAK is lost from pericytes, it increases the expression of another protein called Axl. Increased levels of Axl trigger several signalling pathways that enhance angiogenesis and tumour progression.
The team looked at clinical samples of human melanoma and found that they were able to stratify patients based on their pericyte FAK level. When pericyte FAK was absent in a large proportion of tumour blood vessels in the sample, tumour growth and progression were increased, indicating that pericyte FAK has a protective role in cancer.
The study supports the established idea that pericyte-targeted therapy may be important in anti-cancer treatment, and the signalling pathways involved in the cross-talk between pericytes and tumour cells identified in this study may represent new targets for treatment. The team will now examine whether pericyte FAK also has a role in controlling metastasis - the spread of cancer from one site in the body to another.
This research was performed in collaboration with researchers from the Institute of Cancer Research, Champalimaud Centre for the Unknown (Lisbon, Portugal), Sun Yat-Sen University (Guangzhou, China), the University of Edinburgh, King’s College London and Queen Mary’s Blizard Institute.