Runx2 is expressed in human glioma cells and mediates the expression of galectin-3

Runx2 is a member of the Runx family of transcription factors (Runx1-3) with a restricted expression pattern. It has so far been detected predominantly in skeletal tissues where, inter alia, it regulates the expression of the P-galactoside-specific lectin galectin-3. Here we show that, in contrast to Runx3, Runx1 and Runx2 are expressed in a variety of human glioma cells. Runx2 expression pattern in these cells correlated completely with that of galectin-3, but not with that of other galectins. A similar correlation in the expression pattern of galectin-3 and Runx2 transcripts was detected in distinct types of 70 primary neural tumors, such as glioblastoma multiforme, but not in others, such as gangliocytomas. In glioma cells, Runx2 is directly involved in the regulation of galectin-3 expression, as shown by RNAi and transcription factor binding assays demonstrating that Runx2 interacts with a Runx2-binding motif present in the human galectin-3 promoter. Knockdown of Runx2 was thus accompanied by a reduction of both galectin-3 mRNA and protein levels by at least 50%, dependent on the glial tumor cell line tested. Reverse transcriptase-polymerase chain reaction analyses, aimed at finding other potential target genes of Runx2 in glial tumor cells, revealed the presence of bone sialoprotein, osteocalcin, osteopontin, and osteoprotegerin. However, their expression patterns only partially overlap with that of Runx2. These data suggest a functional contribution of Runx-2-regulated galectin-3 expression to glial tumor malignancy. (C) 2008 Wiley-Liss, Inc.