Spread of tumours ‘related to blood protein’
A team of scientists has found that a protein involved in promoting tumour growth and survival is also activated in surrounding blood vessels, enabling cancer cells to spread into the bloodstream. The investigation was undertaken by principal investigator Dr David D. Schlaepfer of the University of California (UC).
Blood vessels are tightly lined with endothelial cells, which form a permeability barrier to circulating cells and molecules. Schlaepfer explained: “Our studies show that pharmacological or genetic inhibition of the endothelial protein focal adhesion kinase, or FAK, prevents tumour spread by enhancing the vessel barrier function.”
The researchers found that selective FAK inhibition within endothelial cells prevented spontaneous tumour metastasis without alterations in tumour size. Schlaepfer, with colleagues at the UC San Diego Moores Cancer Center, is exploring whether inhibiting targets like FAK, which has important regulatory functions in both tumour cells and blood vessels, might provide a dual mechanism for preventing both cancer growth and spread.
Using mouse models of breast, ovarian, and melanoma tumours, first author Dr Christine Jean showed that FAK activity was elevated in the blood vessels surrounding tumours, compared to normal tissue. FAK modifies the function of other cellular proteins and researchers identified a previously unknown FAK target: a protein called vascular endothelial cadherin (VE-cadherin) that helps endothelial cells fasten tightly together.
When modified by FAK, VE-cadherin complexes fall apart and blood vessels become leaky. Inactivating FAK within endothelial cells prevented this unwanted permeability and helped block the ability of tumour cells to pass through endothelial cell barriers.
Schlaepfer said the research has major clinical implications. Metastasis – the spread of a cancer from its originating site to other parts of the body – is responsible for 90% of cancer-related deaths. He noted that several FAK-inhibitors are currently being tested in clinical trials.
The findings have been published in the Journal of Cell Biology and were part funded by the European Research Council.
