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Attractin Is Elevated in the
Cerebrospinal Fluid of Patients with Malignant Astrocytoma and
Mediates Glioma Cell Migration
Fatima W. Khwaja1,
Jonathan S. Duke-Cohan3,
Daniel J. Brat2
and Erwin G. Van Meir1
Authors' Affiliations: 1
Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery
and Hematology/Oncology, Winship Cancer Institute, and 2
Department of Pathology and Laboratory Medicine, Emory University
School of Medicine, Atlanta, Georgia; and 3 Department of
Medical Oncology, Dana-Farber Cancer Institute, and Department of
Medicine, Harvard Medical School, Boston, Massachusetts -- Requests
for reprints: Erwin G. Van Meir, Winship Cancer Institute, Emory
University, 1365C Clifton Road Northeast, C5078, Atlanta, GA 30322.
Phone: 404-778-5563; Fax: 404-778-5550; E-mail: evanmei@emory.edu.
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Purpose.
There are a limited number of noninvasive methods available for
the monitoring of neoplastic disease in the central nervous system.
The goal of our study was to find reliable
markers that could be used for disease monitoring as well
as to identify new targets for the therapeutic intervention
for malignant astrocytoma (WHO grades 3 and 4).
Experimental Design. We
employed proteomic techniques to identify secreted proteins
in the cerebrospinal fluid that were specific to patients
with malignant astrocytoma.
Results. Among 60
cerebrospinal fluid samples of patients with various
central nervous system diseases, attractin was consistently found
to be elevated in the samples of patients with malignant astrocytoma.
To independently validate these results,
we examined attractin expression in a new set of 108 normal
and tumoral brain tissue specimens and found elevated
expression in 97% of malignant astrocytomas, with the
highest levels in grade 4 tumors.
Using immunohistochemistry, we further
showed that attractin is produced and secreted by the tumor
cells.
Finally, we showed that
cerebrospinal fluid from brain tumor patients induces
glioma cell migration and that attractin is largely responsible
for this promigratory activity.
Conclusions. Our results
find attractin to be a reliable secreted marker for
high-grade gliomas.
Additionally, our migration studies suggest
that it may be an important mediator of tumor invasiveness, and
thus, a potential target in future therapies.
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