A particular white blood cell plays a direct role in the development and spread of cancerous tumours, scientists at The Scripps Research Institute have shown.
Research Professor James Quigley, staff scientist Elena Deryugina, and colleagues had previously demonstrated that white blood cells known as neutrophils—bone marrow-derived cells that function as “first responders” at sites of acute inflammation—promote the growth of new blood vessels in normal, healthy tissue.
The team has now tied these cells to the induction and growth of new blood vessels in malignant tumours and to the spread of tumour cells through those newly formed vessels. The scientists have also uncovered some of the mechanisms underpinning this process—which could be interrupted by properly targeted drugs.
The Scripps team has been particularly interested in neutrophils, in part because several studies have demonstrated a link between elevated neutrophil levels and high rates of tumour invasion among cancer patients. Mounting evidence has also indicated that neutrophils play a particularly important role during the early stages of tumour development.
“During tumour development, neutrophils appear to be one of the first inflammatory cell types on the scene,” said Deryugina, who spearheaded the new study.
In a series of cleverly designed experiments, Quigley, Deryugina, and colleagues established a link between neutrophils, their MMP-9, and the growth and spread of tumours.
The scientists alternately raised and lowered the quantity of neutrophils allowed to flow into two different kinds of early-stage tumors, which had been transplanted into chicken embryos and mice. They also introduced several different versions of the enzyme, sometimes combining it with dampening agents, sometimes not.
By observing the subsequent decrease and increase in the formation of new blood vessels, the Scripps Research team was able to establish that the unique form of the enzyme delivered by neutrophils was directly responsible for heightening the growth of new blood vessels in the tumours. Just as importantly, they were able to determine that the newly formed blood vessels served as “escape routes” or conduits for the spread of tumour cells beyond their initial location.
The study has been detailed in the American Journal of Pathology.