Skog et al., Nature Cell Biology

In a bubble. Tracking tiny vessicles of genetic material emitted by tumor cells could help doctors better diagnose and treat brain cancer patients.

Tumor Secrets Written in Blood

Doctors may soon be able to use blood tests rather than invasive biopsies to figure out what type of brain tumors their patients have. The findings, which come thanks to new insights about how tumor cells communicate with their environment, may also bring physicians closer to the goal of more personalized medicine.

Cells are chatty, constantly exchanging proteins or electrical signals with their neighbors. For example, tumor cells can signal nearby blood vessels to grow in their direction, thereby facilitating tumor growth. Previous research has shown that many cells, including cancer cells, communicate directly with one another by emitting tiny bubbles of cellular material called microvesicles. Their importance for communication between breast cancer cells prompted Johan Skog, a geneticist at Harvard Medical School in Boston, and colleagues to examine microvesicles secreted by glioblastoma, or brain tumor, cells.

Previous research had analyzed the protein and lipid content of glioblastoma microvesicles. But upon closer examination, the researchers also detected pieces of RNA. That made Skog and neurologist Xandra Breakefield, also of Harvard Medical School, wonder whether they could develop some sort of test for this genetic material. "We kind of had this wild idea that because these tumor cells are just pouring [out microvesicles], maybe we can actually see it in the blood," Breakefield says.

To test their hunch, the researchers isolated microvesicles from 30 frozen tumor samples and looked for mRNA from a particular growth receptor unique to glioblastomas. The mRNA was present in nearly half of the tumor samples and in 28% of blood samples that had been drawn from patients at the same time, the researchers report online this week in Nature Cell Biology.

Twenty-eight percent might seem like a low number, the researchers say, but it's significant given that RNA can degrade over time, so fresher samples would likely be more accurate. Comparing proteins within the microvesicles with the originating tumors showed that the vesicles also accurately reveal the protein content of the tumors, providing still more information about how tumors might respond to specific therapies, the researchers report. With further refinement, such tests will allow doctors to tell what kind of genetic mutations their patients' tumors may contain, which can help them select the best treatment for the patient, Breakefield says.

That would be a huge boon for therapy by allowing doctors to combine visual imaging, such as MRI scans, of tumors with knowledge of their genetic make-up, says experimental oncologist Janusz Rak of McGill University Health Centre in Montreal, Canada. "It's not going to replace imaging, but it can complement imaging in extremely powerful and interesting way."

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