Protein destroys migrating cancer cells on contact

Date: Jan-09-2014In a study published online this week in the Proceedings of the National Academy of

Sciences, a US team of biomedical engineers demonstrates a way to stop migrating cancer cells

dead in their tracks as they travel through the bloodstream to set up new tumors.

Metastasis is where cancer cells from a first tumor detach and spread to other parts of the

body.

Surgery and radiation are usually quite effective for treating primary tumors, but once

cancer cells start migrating the chances of successful treatment worsen considerably, partly

because they are difficult to track down. The vast majority of deaths from cancer are due to

metastasis.

Now, a new study suggests it is possible not only to locate these migrating cancer cells, but
to annihilate them before they have a chance to set up secondary tumors.

Senior author Michael

King, a professor of biomedical engineering at Cornell University, Ithaca, New York, explains:

"These circulating cancer cells are doomed. About 90% of cancer deaths are related to

metastases, but now we've found a way to dispatch an army of killer white blood cells that cause

apoptosis - the cancer cell's own death - obliterating them from the bloodstream. When surrounded

by these guys, it becomes nearly impossible for the cancer cell to escape."

For their study, the Cornell team used human blood samples and later, mice, to test the effect of two proteins: an

adhesive called E-selectin, and another protein called TRAIL (Tumor Necrosis Factor Related

Apoptosis-Inducing Ligand - a protein that triggers suicide in tumor cells).

Cancer cells 'kill themselves' when in contact with TRAIL-coated white blood cells

Together the two proteins formed a sticky coating around leukocytes - white blood cells found

everywhere in the bloodstream.

They found that once cancer cells came into contact with the sticky white blood cells, they

imploded.

One surprising factor was that the chaotic environment of a flowing medium, the bloodstream,

actually improved the chances this would happen. When they tested the approach in a still medium,

it was not as effective.

And targeting the cancer cells directly with proteins, was not as effective either. It seems the

best way was to turn the white blood cells into sticky carriers of the killer TRAIL protein.

For instance, when they targeted the cancer cells in saline directly with the proteins, the

success rate was 60%.

But when they tried again with a model of flowing blood that has forces, mixing and other

conditions similar to the human body, the kill rate shot up to 100%.

The authors write:

"The mechanism is surprising and unexpected in that this repurposing of white blood cells in

flowing blood is more effective than directly targeting the cancer cells with liposomes or soluble

protein."

Funds from the National Cancer Institute of the National Institutes of Health helped finance

the study.

Meanwhile in another study published recently in Cell, another US team described how

they stopped the first step of breast

cancer spread in mice.

They discovered that by knocking out a protein in a class of cells that leads the migration,

they could render them incapable of carrying out the first crucial step of metastasis.

Written by Catharine Paddock PhD

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