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

摘要

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