Tiny Sacs Released By Cancer Cells May Offer Effective Cure for Brain Tumour

by VR Sreeraman on Nov 18 2008 2:47 PM

Massachusetts General Hospital (MGH) researchers say that brain tumour cells release tiny sacs called microvesicles, which contain information that may prove helpful in developing an effective treatment for the disease.

The researchers claim that they have found tumour-associated RNA and proteins in membrane microvesicles called exosomes in blood samples from glioblastoma patients.

Upon deeply analysing exosome contents, say the researchers, they could identify factors that could facilitate a tumour's growth through delivery of genetic information or proteins, or signify its vulnerability to particular medications.

"Glioblastomas release exosomes in sufficient quantities to pass the blood-brain barrier. We were able to isolate them, analyze the RNA transcripts and show how they might be used as biomarkers to guide targeted therapy and monitor treatment response," Nature Cell Biology quoted Dr. Johan Skog, who works in the laboratory of Dr. Xandra Breakefield at the MGH Neuroscience Center, as saying.

"Exosomes also may someday be used to deliver therapeutic molecules to the site of a tumour," added the study's lead author.

The research team claim that they are the first to carefully analyse the contents of exosomes shed from glioblastoma cells, and characterize their contents.

During the study, the researchers first analysed tumour cells from three glioblastomas, and verified that the cells released exosomes containing RNA and protein molecules.

The team observed that some messenger RNAs related to activities like cell proliferation and migration, angiogenesis, and immune response were highly abundant in the exosomes.

Upon culturing glioblastoma exosomes with normal cells, they saw that tumour RNA was delivered into the normal cells and generated its encoded protein, supporting the role of exosome-delivered RNA in manipulating the cellular environment.

The researchers then analysed tumour tissue and blood serum from 25 glioblastoma patients to determine the potential of glioblastoma exosomes as markers of a tumour's genetic makeup.

They said that their efforts enabled them to find tumour exosomes and to identify, in some tissue samples, a mutation in the epidermal growth factor receptor (EGFR) gene that characterizes a tumour subtype.

The group revealed that in two patients, an EGFR mutation that did not appear in the tumour tissue sample was identified by exosome analysis, reflecting how a surgical biopsy could miss tissue conveying critical information because of the often-chaotic diversity of cells within a tumour.

"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," says Skog, who is an instructor in Neurology at Harvard Medical School.

"Detecting mutational profiles through a noninvasive blood test could allow us to monitor how a tumor's genetic makeup changes in response to therapy, which may necessitate changes in treatment strategy," he adds.

The researchers are currently researching into the role of exosomes in other solid tumours. Their aim is to find out how exosomes may help monitor additional tumour-associated mutations.