New Biomarkers For Brain Tumor Discovered

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Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;  Genetics;  Blood / Hematology
Article Date: 18 Nov 2008 - 11:00 PST

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Researchers in the US and The Netherlands have discovered that cancer cells from a deadly type of human brain tumor called glioblastoma release tiny sacs containing proteins that traverse the brain-blood barrier and contain genetic material that could be used as biomarkers in new diagnostic tools and perhaps as new targets for treatments too.

The study, which was was published online on 16 November in the journal Nature Cell Biology, was the work of lead author Dr Johan Skog, who works in the laboratory of co-author Dr Xandra Breakefield, at the Neuroscience Centre of Massachusetts General Hospital (MGH), which is part of Harvard Medical School, and colleagues from other parts of Harvard Medical School and the Cancer Center Amsterdam.

Using blood samples from glioblastoma patients, Skog, Breakefield and colleagues found that the glioblastoma cells released tiny blood-borne sacs called microvesicles or exosomes that carry a range of proteins and tumor-associated RNA.

Some of these glioblastoma microvesicles or exosomes contained the cancer genes EGFRvIII and miRNA-21 that cause cells to proliferate, leading the researchers to suggest that they may serve as new biomarkers or drug targets for this deadly form of cancer.

Skog explained in a press statement that glioblastomas shed enough exosomes to pass the blood-brain barrier and he and his colleagues were able to isolate them and:

"Analyze the RNA transcripts and show how they might be used as biomarkers to guide targeted therapy and monitor treatment response."

"Exosomes also may someday be used to deliver therapeutic molecules to the site of a tumor," he added.

Exosomes are a normal part of cell to cell communication and scientists were already aware that when tumors shed them they can change the environment of cells to make it easier for tumors to grow. But this study's unique contribution is that it identifies the specific markers that do this for glioblastoma.

For the study the researchers looked at tumor samples from three glioblastomas and found they shed exosomes carrying lots of proteins and RNA molecules that are important for cell proliferation and migration, development of blood vessels, and immune response.

Then they cultured the exosomes from the glioblastomas with normal (non cancerous) cells and found that they transferred tumor-linked RNA molecules (ie genetic material) into the normal cells which then started to make new proteins which are like the ones that help the exosome-delivered RNA to change the environment of cells.

The researchers also analyzed tumor tissue and blood samples from 25 glioblastoma patients to study how glioblastoma exosomes might serve as genetic biomarkers of a tumor. This is how they found the EGFRvIII and miRNA-21 cancer genes. In two of the patients the EGFR mutation did not show up in the tumor sample but it was found in their blood samples, showing how it could be possible for a surgical biopsy to show a false negative.

Skog, who is also an instructor in Neurology at Harvard Medical School said:

"It is known that the effects of some anticancer drugs depend on a tumor's genetic mutational profile, so our results have broad implications for personalized medicine."

He said it might be possible to use this method to fine tune treatments by using blood tests to monitor how a tumor's genetic profile changes in response to drugs.

In the meantime Skog, Breakefield and colleagues are investigating whether exosomes shed by other types of tumor may also have similar properties and therefore open new doors to tumor diagnosis and treatments.

"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers."
Johan Skog, Tom Würdinger, Sjoerd van Rijn, Dimphna H Meijer, Laura Gainche, William T Curry, Jr, Bob S Carter, Anna M Krichevsky and Xandra O Breakefield.
Nature Cell Biology, published online 16 November 2008.
doi:10.1038/ncb1800

Click here for Abstract.

Sources: Journal Abstract, Massachusetts General Hospital.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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