Thursday, 9 January 2014

'Piggy-backing proteins' could kill cancer cells

'Piggy-backing proteins' could kill cancer cells “Cancer-killing "sticky balls" can destroy tumour cells in the blood and may prevent cancers spreading,” BBC News reports.
The headlines follow a laboratory study which found that “piggy-backing” two proteins to white blood cells caused cancer cells to die.
Cancer can spread in three ways; directly, via the lymphatic system, and through the blood. The latter is particularly dangerous, as if cancer spreads through the blood it can spread from one part of the body to others, such as from the lungs and into the brain (this is known as metastasis).
Metastatic cancer is responsible for 90% of cancer-related deaths, and currently, we have only limited ways to stop the spread of blood-borne cancer cells.
This study made use of two proteins normally found on the surface of a type of white blood cell called “natural killer cells” which kill abnormal and infected cells. In the laboratory, these two proteins were mixed with human blood and stuck to other types of white blood cells that could target cancerous cells.
These “retrofitted” white blood cells were then injected into mice that had been exposed to the type of abnormal cells associated with colon and prostate cancer in humans.
Encouragingly, a significant number of the cancer cells died.
While this is an exciting new avenue of animal research, there are many more steps to take before such a treatment could be used to prevent the spread of tumours in cancer patients. 

Where did the story come from?

The study was carried out by researchers from Cornell University and was funded by the Cornell Centre on the Microenvironment and the National Cancer Institute.
The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences (PNAS) of the United States of America. The study has been published on an open access basis so it is free to read online or download as a PDF.
Generally the media reported the story accurately, though The Daily Telegraph was over-optimistic that the method could “prevent 90 per cent of deaths”. This is the estimated number of cancer deaths due to metastasis, but even if this new technique could reduce the spread of cancer in the blood stream, many cancers are first diagnosed at a late stage, after they have metastasised. 

What kind of research was this?

This was a laboratory study that looked at the effect on cancer cells of white blood cells with two proteins attached to their surface. The researchers aimed to see how many cancer cells were affected by using both human blood samples, and live mice. This was an early stage study in the long process of developing new treatments for cancer. 

What did the research involve?

The researchers initially mixed cancer cells in a solution with two different proteins that are usually present on a certain type of white blood cell called “natural killer cells”.
These cells are part of the immune system, and as their name implies, they have a role in killing abnormal and infected cells.
The two proteins normally found on natural killer cells are called TNF-related apoptosis inducing ligand (TRAIL), and E-selectin adhesion receptor (ES). The researchers found that cancer cells were more likely to die if they were exposed to both proteins at once.
The researchers then added both proteins (ES/TRAIL) to human blood samples and found that they stuck to the surface of other types of white blood cells. They called these “unnatural killer cells”.
Still in the laboratory, they mixed colorectal cancer cells and prostate cancer cells into the blood under “flow” conditions so that the cells would bump into each other, mimicking blood circulation.
The researchers then injected colorectal cancer cells into the blood circulation of mice. After 30 minutes they injected either ES/TRAIL, ES or TRAIL. They measured the number of cancer cells left after two and a half hours, and looked at how many cancer cells had been deposited in the lungs. 

What were the basic results?

In a human blood sample in the laboratory:
  • less than 5% of the cancer cells remained after ES/TRAIL treatment
  • the rate of cancer cell death was much higher than when cancer cells were just mixed with the proteins without the blood
  • adding ES/TRAIL proteins to the surface of white blood cells did not cause the white blood cells to die over 24 hours 
  • ES/TRAIL proteins did not have an effect on the lining of blood vessels
In mice:
  • after two and a half hours, mice injected with ES/TRAIL had less than 2,000 cancer cells per ml of blood compared to mice injected with just ES, who had roughly 130,000 cancer cells per ml of blood
  • half as many cancer cells were found in the lungs of the mice treated with ES/TRAIL
  • ES/TRAIL proteins attached to the surface of white blood cells without causing any obvious problems 

How did the researchers interpret the results?

The researchers concluded that this study “represents an important first step toward the targeting of circulating tumour cells in the bloodstream as a means to prevent cancer metastasis. Clinically, for instance, one could envision using these liposomes as a preventive measure upon diagnosis of highly metastatic hematogenous cancers [those with a high propensity to spread via the bloodstream] such as those originating in breast, prostate and lung”. 


This laboratory study has shown that white blood cells do not seem to be harmed when two proteins usually found on the surface of a particular immune cell with a role in killing abnormal cells are attached. Encouragingly, it showed that doing this can cause cancer cells to die in human blood samples. Similar results were found when these two proteins and cancer cells were injected into the blood circulation of live mice.
These are exciting early results suggesting these proteins could have the potential to be developed into a trial treatment that may be able to prevent cancer cells spreading via the bloodstream. However, much further research will be needed to determine the risks and harms of such an approach before any testing can be conducted in humans.
The media suggests that such a treatment could “prevent 90 per cent of deaths”. This figure is the estimated number of cancer deaths that are due to metastasis. However, even if this new technique could reduce the spread of cancer in the bloodstream, many cancers are first diagnosed at a late stage, after they have metastasised.
Overall, it is far too early to suggest that this treatment could save the lives of people who would otherwise die as a result of cancer spread to other organs of the body (metastases).
With these caveats in mind this is genuinely exciting research. While there is currently no guarantee that it will lead to effective treatments in humans, novel approaches that could be used to combat cancer are always welcome.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

'Sticky balls' may stop cancer spreading. BBC News, January 7 2014

Links To Science

Mitchell MJ, Wayne E, Rana K, et al. TRAIL-coated leukocytes that kill cancer cells in the circulation. PNAS. Published online January 6 2014

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