Previously, in clinical glioma specimens, we found decreased expression of VX-770 clinical trial BMPR-IB mRNA

and protein in malignant glioma tissues compared to the levels in normal brain tissues and benign glioma tissues, whereas the expression of other molecules in the signaling pathway of BMPs/Smad1/5/8 remained consistent. We also found an inverse correlation between the protein and mRNA expression levels of BMPR-IB and malignancy grade [5]. From these clinical results, we assumed that BMPR-IB must be involved in the development of glioma. So, in our present study, we selected several malignant human glioblastoma cell lines that have different expressions of BMPR-IB to study the functional role of BMPR-IB in the development of glioma. Because the Selleckchem SP600125 malignant human glioma cell lines that we selected have different expression levels of BMPR-IB, they are suitable as subjects for the study of the functional roles of BMPR-IB in vitro. Hyperproliferation is a hallmark of glioblastoma multiforme. Our present study showed that BMPR-IB

overexpression decreased the anchorage-independent growth of U87 and U251 glioblastoma cells, which present a lower expression of BMPR-IB in vitro. Further, the reduced BMPR-IB expression caused an increase in the number of SF763 colonies that express higher levels of BMPR-IB compared to other glioma cell lines. Additionally, FACS analysis showed PX-478 that this effect was at least partially caused by the inhibition of glioma cell cycle progression at the G0/G1 transition (Figure 2B 3B). These data suggest that BMPR-IB protein plays an inhibitory role in the development

of glioblastoma and might be a key regulator of the G1-S transition in glioblastoma cells. A recent study by Piccirillo et al. has also shown that BMP4 may act as a key inhibitory regulator cAMP of tumor-initiating, stem-like CD133+ cells from GBMs. However, those authors did not address the aberrant expression of BMPR-IB in the primary tumor-initiating cells that were derived from GBM tissues [16]. We detected the expression of CD133 in U251/U87/SF763 cell lines, and found that most of these cells were CD133- (Additional file 1: Figure S 2). So, the tumor inhibited effects of BMPR-IB in our study are on those glioblstoma cells that express a low level of BMPR-IB, but are not limited to the fraction of cells with a stem cell-like phenotype (CD133+ cells) as reported by Piccirllo. et al. It has been reported that BMP2/4 acts as a neuroepithelial proliferation signal at very early stages of embryonic central nervous system development, an effect mediated principally by BMPR1A [17, 18]. Later in the development of the central nervous system, BMP2/4 induces neuronal and astrocytic differentiation of NSCs, an event that coincides with increased expression of BMPR1B [19, 20]. Another study by Lee et al. has shown that BMPR-IB was able to induce the differentiation of a kind of gliomblastoma initiated cell [21].