Reduced expression of the hyaluronan and proteoglycan link proteins in malignant gliomas.

Abstract

Malignant gliomas have a distinctive ability to infiltrate the brain parenchyma and disrupt the neural extracellular matrix that inhibits motility of axons and normal neural cells. Chondroitin sulfate proteoglycans (CSPGs) are among the major inhibitory components in the neural matrix, but surprisingly, some are up-regulated in gliomas and act as pro-invasive signals. In the normal brain, CSPGs are thought to associate with hyaluronic acid and glycoproteins such as the tenascins and link proteins to form the matrix scaffold. Here, we examined for the first time the expression of link proteins in human brain and malignant gliomas. Our results indicate that HAPLN4 and HAPLN2 are the predominant members of this family in the adult human brain but are strongly reduced in the tumor parenchyma. To test if their absence was related to a pro-invasive gain of function of CSPGs, we expressed HAPLN4 in glioma cells in combination with the CSPG brevican. Surprisingly, HAPLN4 increased glioma cell adhesion and migration and even potentiated the motogenic effect of brevican. Further characterization revealed that HAPLN4 expressed in glioma cells was largely soluble and did not reproduce the strong, hyaluronan-independent association of the native protein to brain subcellular membranes. Taken together, our results suggest that the tumor parenchyma is rich in CSPGs that are not associated to HAPLNs and could instead interact with other extracellular matrix proteins produced by glioma cells. This dissociation may contribute to changes in the matrix scaffold caused by invasive glioma cells.

• Authors: Hosung Sim, Bin Hu, Mariano S Viapiano
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 39 Pg. 26547-56 (Sep 25 2009) ISSN: 1083-351X [Electronic] United States
• PMID: 19633295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCAN protein, human
• Brevican
• Chondroitin Sulfate Proteoglycans
• Extracellular Matrix Proteins
• HAPLN2 protein, human
• HAPLN4 protein, human
• Lectins, C-Type
• Nerve Tissue Proteins
• Proteoglycans
• Hyaluronic Acid

Topics

• Adult
• Blotting, Western
• Brain (metabolism)
• Brevican
• Cell Adhesion
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Cell Movement
• Chondroitin Sulfate Proteoglycans (genetics, metabolism)
• Extracellular Matrix Proteins (genetics, metabolism)
• Glioma (genetics, metabolism, pathology)
• Humans
• Hyaluronic Acid (metabolism)
• Lectins, C-Type (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Proteoglycans (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection