Transforming growth factor-β is required for vasculogenic mimicry formation in glioma cell line U251MG

Both vasculogenic mimicry (VM) and transforming growth factor-β (TGFβ) are positively correlated with malignancy in glioma. Accordingly, we supposed that TGFβ might be related with VM, and aimed to detect whether TGFβ could influence VM formation in two glioma cell lines U251MG and SHG44, which were different in malignancy. We found that the VM-positive U251MG had a significantly higher TGFβ expression than the VM-negative SHG44. Downregulating TGFβ in U251MG by RNAi technology resulted in a significantly impaired VM formation, which could be rescued by rhTGFβ. However, adding rhTGFβ could not induce VM in SHG44. To investigate the possible mechanism, we detected the changes of some VM-related genes including EphA2, VE-cadherin, MMP-2, MMP-9, MT1-MMP and LAMC2 by RT-PCR and found that MT1-MMP transcript was affected by TGFβ expression. Gelatin zymography showed a declined MMP-2 activity in the TGFβ-inhibited cells. Further studies showed that MT1-MMP inhibition impaired VM formation in U251MG. Moreover, TGFβ induced MT1-MMP expression and VM formation in a dose-dependent manner. These findings indicated us that TGFβ was required for VM formation in U251MG. MT1-MMP was correlated with TGFβ-induced VM formation. Thus, TGFβ might be a potential target for VM inhibition in glioma.