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Blood Cells Retrieve Information From Tumors

Posted on: Monday, 17 November 2008, 09:41 CST

Minute sacs released from tumor cells and flowing in the blood carries genetic knowledge about the tumor, providing a novel way to find and care for the cancer, U.S. researchers announced on Sunday.

"They contain a little piece of the tumor cell in the blood stream. If you just look at these packets, you basically know what kind of mutations are in the tumor cell," stated Xandra Breakefield of Massachusetts General Hospital in Boston, whose findings are published in the journal Nature Cell Biology.

These membrane-covered sachets, called exosomes, symbolize a brand new way of retrieving information about cancer, presenting ways to choose the most effective therapy, viewing how a patient reacts to treatment, and maybe finding a way to transport therapies directly to the tumor, Breakefield said.

Massachusetts General Hospital (MGH) researchers explain in the study how they discovered the tumor-associated RNA and proteins in membrane microvesicles labeled exosomes in blood samples taken from glioblastoma patients.

"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," says Johan Skog, PhD, who works in the laboratory of Xandra Breakefield, PhD, at the MGH Neuroscience Center. "Exosomes also may someday be used to deliver therapeutic molecules to the site of a tumor," he said.

"It's a whole new concept of cell communication we didn't know tumors used," Breakefield added.

She said for many kinds of cancer, there is not a sure way of knowing what genetic mutations are specific to the tumor, simply from taking a sample and performing a biopsy.

Several blood tests, like prostate specific antigen, or PSA, look for prostate cancer by simply examining the blood for increased levels of an exact protein.

Via the exosomes, doctors could retrieve explicit information about a cancer from an easy blood test.

"It's a blood biomarker," Breakefield said.

Several types of cells emit exosomes in their regular cell-to-cell communiqué, and many types of tumors are acknowledged to discard exosomes having proteins that can change the cellular surroundings to help tumor growth. The investigation is supposed to be the first to circumspectly examine the insides of exosomes dropped from glioblastoma cells and describe the contents.

"It's a form of cell communication that normal cells use but tumor cells use with a vengeance," Skog said.

For the study, researchers choose to analyze the exosomes dropped from glioblastoma cells. Glioblastoma is a very hostile kind of brain cancer.

Inside the cells they discovered remains of genetic messenger ribonucleic acid, or RNA, as well as cell messengers linked to cell development, immune response and the creation of new blood vessels.

When researchers married the exosomes to regular cells in the lab, the tumor RNA communicated its genetic message to the cells.

"That is important to know. We didn't realize they had this external means of communicating with their surroundings," Breakefield said.

The team also reviewed the blood and tissue samples from 25 brain cancer patients. They could not locate tumor exosomes in both. In two patients, this study found a specific genetic mutation in the epidermal growth factor receptor, or EGFR, gene that a mere surgical biopsy had not discovered.

“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," explains Skog.

"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 added.

Skog, Breakefield and their colleagues are also inspecting the role of exosomes in other kinds of tumors and how they could monitor further tumor-associated mutations.

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On the Net:

• Massachusetts General Hospital
• Nature Cell Biology

Source: redOrbit Staff & Wire Reports

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