Bone morphogenesis proteins (BMP2) are members of the transforming growth factor beta superfamily which includes multifunctional peptides that regulate cell proliferation, differentiation and other functions in many cellular systems. BMP2 is associated with the regulation of proliferation, survival and self-renewal of stem cells. BMP2 binds to a receptor complex composed of type I and type II BMP2 receptors, which are membrane-spanning serine/threonine kinases and activate downstream Smad proteins. Using a 35,000 element custom cDNA microarray chip, enriched for glial tumor transcripts, we found that BMP2 was highly expressed in astrocytic tumors as compared to normal brains, whereas no differences in the expression of BMP6 and BMP7 were observed. These data were further validated by RT-PCR and Western blot analysis. Similarly, we found that glioma cell lines expressed significantly higher levels of BMP2 as compared to normal human astrocytes. In contrast to the enhanced expression of BMP2 in gliomas, the receptors BMP2RI and BMP2RII were similarly expressed in gliomas and normal brains. Using statistical analysis we demonstrated that among glial tumor specimens, elevated BMP2 expression was significantly associated with prolonged survival (r=0.33; Cox coefficient=-0.20, p<0.05). To examine the role of BMP2 in glioma cells, we employed siRNAs directed against the BMP2 mRNA. Transfection of glioma cells with BMP2 siRNA induced a decrease in glioma cell proliferation and in their anchorage-independent growth. In addition, silencing of BMP2 reduced the migration of glioma cells and enhanced their attachment on collagen IV, laminin and fibronectin. These results indicate that BMP2 regulates the growth and invasion of glioma cells and that it may represent a novel potential therapeutic target for the treatment of gliomas.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]