B-FABP-expressing radial glial cells: the malignant glioma cell of origin?
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.
Mita
Raja
R
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
Coles
Jeffrey E
JE
Glubrecht
Darryl D
DD
Sung
Rohyun
R
Sun
Xuejun
X
Godbout
Roseline
R
D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor / Q000648:ultrastructure; D002462:Cell Membrane / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000648:ultrastructure; D000071438:Fatty Acid-Binding Protein 7; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins