Hyaluronan regulates ceruloplasmin production by gliomas and their treatment-resistant multipotent progenitors.

Ceruloplasmin (glycosylphosphatidylinositol-linked ferroxidase associated with normal astrocytes) can also be secreted by glioma cells, where its function is unknown. Ceruloplasmin is not only present in glioma cells and in human glioma specimens but also is enriched in highly malignant glioma stem-like cells. Hyaluronan is a large extracellular glycosaminoglycan that enhances malignant glioma behaviors by interacting with CD44 receptors and by downstream activation of signaling proteins and transporters associated with malignancy.

Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors.

Purpose: To determine if hyaluronan oligomers (o-HA) antagonize the malignant properties of glioma cells and treatment-resistant glioma side population (SP) cells in vitro and in vivo.

Experimental Design: A single intratumoral injection of o-HA was given to rats bearing spinal cord gliomas 7 days after engraftment of C6 glioma cells. At 14 days, spinal cords were evaluated for tumor size, invasive patterns, proliferation, apoptosis, activation of Akt, and BCRP expression.