B7-H3 Promotes Migration,invasion And Vasculogenic Mimicry In Lung Adenocarcinoma Through The AKT/MMP14 Signaling Pathway

Background Lung cancer performs in which both morbidity and mortality are at high risk in human cancer and the lung adenocarcinoma is the most common subtype of lung cancer.Lung adenocarcinoma is often accompanied by distant metastases and has a poor prognosis,which makes it challenging to cure patients with it.As a member of the B7-CD28 family,B7-H3 has been described as associated with the progression and exacerbation of a variety of cancers including lung adenocarcinoma,but the mechanism remains unclear.MMP14 belongs to the family of MMPs and plays a role in promoting cancer progression through its collagenase properties.However,the relationship between B7-H3 and MMP14 in lung adenocarcinoma and the specific mechanisms of them are unknown now.Objective To investigate the molecular mechanism of B7-H3 in promoting migration,invasion and vasculogenic mimicry in lung adenocarcinoma.Methods The lung adenocarcinoma cells and the constructed B7-H3 knockout lung adenocarcinoma cells were used in vitro experiment as the research object.The migration,invasion and vasculogenic mimicry of two groups were detected by Transwell and three-dimensional cell culture.The expression of E-cadherin,N-cadherin,Vimentin and VE-cadherin proteins in the two groups was detected by Western-Blot.The correlation between B7-H3 and MMP14,AKT1 and MMP14 was analyzed using TEPIA database,and the correlation between B7-H3 and MMP14,B7-H3 and AKT1 as well as MMP14 was analyzed by Western-Blot.In vivo experiments,the expression of E-cadherin,N-cadherin,Vimentin and VE-cadherin and VE-cadherin in the embedded wax block tissue and the formation of vasculogenic mimicry formation were analyzed by immunohistochemistry in BALB/c nude mouse,which was infected with lung adenocarcinoma cells and B7-H3-KO lung adenocarcinoma cells.Results Compared with lung adenocarcinoma cells,the migration,invasion and vasculogenic mimicry formation of B7-H3-KO cells were reduced,and Western-Blot results showed that the expression of E-cadherin protein was increased while the expression of N-cadherin,Vimentin and VE-cadherin proteins was reduced in B7-H3-KO lung cancer cells.The positive correlation between B7-H3 and MMP14,AKT1 and MMP14 was analyzed in the TEPIA database,meanwhile Western-Blot results showed that there were positive correlations between B7-H3 and MMP14 as well as AKT1 and MMP14.The vivo experiment results showed that E-cadherin was elevated in the BALB/c nude mouse wax block tissue injected with B7-H3-KO lung adenocarcinoma cells,and the expression of N-cadherin,Vimentin and VE-cadherin and the formation of vasculogenic mimicry were decreased.Conclusion In lung adenocarcinoma,B7-H3 positively regulates the expression of MMP14.B7-H3 promotes the migration,invasion and vasculogenic mimicry through the AKT/MMP14 signaling pathway in lung adenocarcinoma.