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

Both vasculogenic mimicry (VM) and transforming growth factor-beta (TGF beta) are positively correlated with malignancy in glioma. Accordingly, we supposed that TGF beta might be related with VM, and aimed to detect whether TGF beta 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 TGF beta expression than the VM-negative SHG44. Downregulating TGF beta in U251MG by RNAi technology resulted in a significantly impaired VM formation, which could be rescued by rhTGF beta. However, adding rhTGF beta 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 TGF beta expression. Gelatin zymography showed a declined MMP-2 activity in the TGF beta-inhibited cells. Further studies showed that MT1-MMP inhibition impaired VM formation in U251MG. Moreover, TGF beta induced MT1-MMP expression and VM formation in a dose-dependent manner. These findings indicated us that TGF beta was required for VM formation in U251MG. MT1-MMP was correlated with TGF beta-induced VM formation. Thus, TGF beta might be a potential target for VM inhibition in glioma.