Combined temozolomide and ionizing radiation induces galectin-1 and galectin-3 expression in a model of human glioma

Abstract

AbstractBackground Despite aggressive treatment for glioblastoma multiforme (GBM), including surgical resection, radiotherapy and temozolomide (TMZ) chemotherapy, over 90% of patients experience tumor recurrence. Galectins are carbohydrate-binding proteins that are overexpressed in the stroma of GBM tumors, and are potent modulators of GBM cell migration and angiogenesis. The objective of this study was to analyze glioma and endothelial cell galectin expression in response to combined chemoradiation. Methodology The effects of TMZ, ionizing radiation, or combined chemoradiation on galectin protein secretion and expression were assessed in U87 orthotopically grown GBM tumors in mice, as well as in vitro in U87 human glioma cells and human umbilical vein endothelial cells (HUVECs). Results We found that combination chemoradiation increased galectin-1 and galectin-3 protein expression in U87 glioma cells. In response to radiation alone, U87 cells secreted significant levels of galectin-1 and galectin-3 into the microenvironment. HUVEC co-culture increased U87 galectin-1 and galectin-3 protein expression 14 - 20% following chemoradiation, and conferred a radioprotective benefit to U87 glioma cells. In vivo, radiation alone and combination chemoradiation significantly increased tumor galectin-1 expression in an orthotopic murine model of GBM. Conclusions Glioma cell galectin expression increased following combined chemoradiation, both in vitro and in vivo. The presence of endothelial cells further increased glioma cell galectin expression and survival, suggesting that crosstalk between tumor and endothelial cells in response to standard chemoradiation may be an important factor in mediating glioma recurrence, potentially via galectin upregulation.