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PMID: 17898869 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

B-FABP-expressing radial glial cells: the malignant glioma cell of origin?

Neoplasia (New York, N.Y.) ·Vol. 9 ·No. 9 ·2007-09-00 ·Pages 734-44

Mita R, Coles JE, Glubrecht DD, Sung R, Sun X, Godbout R

Abstract

Brain fatty acid-binding protein (B-FABP) is normally expressed in radial glial cells, where it plays a role in the establishment of the radial glial fiber network required for neuronal migration. B-FABP is also expressed in astrocytoma tumors and in some malignant glioma cell lines. To address the role of B-FABP in malignant glioma, we have studied the growth properties of clonal populations of malignant glioma cells modified for B-FABP expression. Here, we demonstrate that expression of B-FABP in B-FABP-negative malignant glioma cells is accompanied by the appearance of radial glial-like properties, such as increased migration and extended bipolar cell processes, as well as reduced transformation. Conversely, B-FABP depletion in B-FABP-positive malignant glioma cells results in decreased migration, reduction in cell processes, and a more transformed phenotype. Moreover, expression of B-FABP in astrocytomas is associated with regions of tumor infiltration and recurrence. Rather than being a direct manifestation of the tumorigenic process, we propose that the ability of high-grade astrocytoma cells to migrate long distances from the primary tumor reflects properties associated with their cell of origin. Thus, targeting B-FABP-expressing cells may make a significant impact on the treatment of these tumors.

Keywords
Astrocytoma brain fatty acid-binding protein infiltration migration radial glia
MeSH Terms
Astrocytoma/metabolism,pathology Brain Neoplasms/metabolism,pathology Carrier Proteins/antagonists & inhibitors,genetics,physiology Cell Adhesion/physiology Cell Differentiation/physiology Cell Division/physiology Cell Line, Tumor/ultrastructure Cell Membrane/ultrastructure Cell Movement/physiology Cell Surface Extensions/ultrastructure Fatty Acid-Binding Protein 7 Glioblastoma/metabolism,pathology Humans Neoplasm Invasiveness/pathology Neoplasm Proteins/antagonists & inhibitors,genetics,physiology Oligodeoxyribonucleotides, Antisense/pharmacology RNA Interference Recombinant Fusion Proteins/antagonists & inhibitors,physiology Tumor Suppressor Proteins/antagonists & inhibitors,genetics,physiology
Chemicals
Carrier Proteins FABP7 protein, human Fatty Acid-Binding Protein 7 Neoplasm Proteins Oligodeoxyribonucleotides, Antisense Recombinant Fusion Proteins Tumor Suppressor Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Mita Raja
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
Coles Jeffrey E
Glubrecht Darryl D
Sung Rohyun
Sun Xuejun
Godbout Roseline
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1476-5586
DOI
10.1593/neo.07439
Published
2007-09-00
Pages
734-44
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1993858
Subset
IM
External Links
PubMed source DOI: 10.1593/neo.07439 PMC Full Text View journal details
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