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

Neoplasia. 2007 Sep;9(9):734-44. doi: 10.1593/neo.07439.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / metabolism
  • Astrocytoma / pathology*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / 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
  • Glioblastoma / pathology*
  • Humans
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • RNA Interference
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / physiology
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*

Substances

  • Carrier Proteins
  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • Neoplasm Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins