Newly identified biomarker detects and regulates spread of brain tumors

ATLANTA -- Researchers at Emory University's Winship Cancer Institute have identified a novel biomarker for brain tumors and have uncovered a potential role the marker may play when the tumor spreads or comes back after treatment. The study, “Attractin is elevated in the cerebrospinal fluid of patients with malignant astrocytoma and mediates glioma cell migration," is published in the November issue of Clinical Cancer Research.

The biomarker, a protein known as "soluble attractin," is normally absent in the central nervous system (CNS) and is undetectable in cerebral spinal fluid (CSF), unless malignant astrocytomas--the most common form of intracranial tumors--are present in the CNS. The CSF is a liquid that bathes the brain and acts as a reservoir, which can be sampled for analysis of proteins secreted by CNS tumors.

This newfound ability to reliably identify biomarkers for malignant astrocytomas means that physicians will have a new minimally invasive method to track the success of treatments. These biomarkers, singly or in combination, will provide a fingerprint of the disease and be able in the future to better define the disease, predict what kind of treatment to use and allow doctors to monitor how well the tumor responds to treatment.

"Using proteomic analyses of the CSF of patients with brain tumors, we have identified for the first time that attractin levels are elevated in patients with high-grade astrocytoma," says Erwin Van Meir, PhD, professor of neurosurgery and hematology/oncology and lead author of the study. "Because few noninvasive methods are available for monitoring CNS malignancies, there is an urgent need to find reliable indicators."

Van Meir and his colleagues analyzed 60 cerebrospinal fluid or cyst fluid samples from patients with various CNS diseases using proteomics to examine simultaneously all proteins in biological samples. To validate the study's results, attractin levels in a set of 100 normal and tumoral brain samples also were examined. The researchers found elevated attractin levels in 97 percent of malignant astrocytomas, with the highest levels in grade IV tumors.

The grade of a tumor reflects the level of abnormality its cells exhibit and how quickly the tumor is likely to grow and spread and is a predictor of patient outcome. Low-grade tumors are slow growing and show little abnormality, whereas high-grade tumors are highly abnormal and grow and spread quickly, making treatment more difficult. Patients with highly malignant astrocytomas typically have a life expectancy of about one year even after neurosurgery, chemotherapy, and radiation therapy, highlighting the pressing need for more research to develop improved therapies.

Equally important, the researchers also found that attractin plays a key role in the motility of the cancer cells, which influences their ability to spread in the brain, a major cause of recurrence of malignant astrocytoma. Secreted by the tumors themselves, attractin induces cancer cells to migrate, although that mechanism is not well understood. Knowing that attractin modulates the migration and possibly the recurrence of these tumors makes it a promising target for future therapeutic intervention, says Dr. Van Meir. "Our studies suggest that measuring attractin levels in patients with grades II-IV astrocytoma should be explored further as a potential biomarker for monitoring the growth of these tumors or as a potential new target for therapy."

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This study, which was conducted in collaboration with the Dana Farber Cancer Institute, was funded by the National Institutes of Health, the Genetics and Molecular Biology Program of Emory University's Graduate Division of Biological and Biomedical Sciences, and the National Science Foundation. The team of researchers from Emory included Dr. Van Meir, Fatima W. Khwaja, PhD, Daniel Brat, MD, PhD; and Harvard Medical School's Jonathan Duke-Cohan, PhD.


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