Knockdown of metadherin inhibits vasculogenic mimicry in breast cancer

Vasculogenic mimicry (VM) contributes to the resistance of anti angiogenic therapies in breast cancer. It has been reported that metadherin (MTDH) was associated with angiogenesis in breast cancer. However, the association between MTDH and VM formation is still unknown. The present study investigated the effects of MTDH downregulation on VM formation in the breast cancer and the potential underlying mechanisms of action. A Matrigel based tube formation assay was performed to evaluate VM formation. Reverse transcription quantitative PCR and western blot analysis were conducted to investigate the mRNA and protein expression levels of AKT, VEGF, VE-cadherin and EphA2. CD31/Periodic Acid Schiff double staining was performed to detect VM vessel formation. Following MTDH knockdown in MDA-MB-231 cells, the formation of VM was significantly decreased in vitro and ex vivo. In addition, the expression levels of AKT, VEGF, VE-cadherin and EphA2 in MDA-MB-231 cells were decreased compared with the control group. These results show that knockdown of MTDH could significantly inhibit the VM in breast cancer and may be partially related to the regulation of VEGF through AKT signal way.