The Role Of TNF-α In The Process Of Epithelial Mesenchymal Transition Induced By α Particles

Epithelial mesenchymal transition(EMT)is a biological process that allows a polarized epithelial cell to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype.When cells are going through EMT,expression of adhesion molecules is reduced,cytoskeleton is re-constructed,apoptosis resistance is elevated,and migration capability is enhanced.EMT is an important mechanism for tumor metastasis.Compared with the traditional low linear energy transfer(LET)radiation,ions that have high LET can cause higher numbers and more complicated clustered DNA damages compare with X-ray and γ-ray,of which would result in higher relative biological effectiveness(RBE)such as cell death,gene mutations and cell transformation.It has been found that ionizing radiation can induce epithelial mesenchymal transition of different types of cells,but the underlying mechanisms remain unclear.In this study,human immortalized bronchial epithelial cell line Beas-2B was used to study the role of TNF-α in the process of α particle-induced EMT.The results obtained are as follows:(1)Beas-2B cells irradiated with α particles lost cell-to-cell contacts,changed from a compact epithelial morphology to a spindle-shaped cell morphology,and lost the intercellular adhesion.In the irradiated cells,expression of epithelial cell marker protein E-cadherin was decreased;while expression of mesenchymal cell marker proteins vimentin and fibronectin were increased.In addition,β-catenin was transferred from cytosol to the nucleus.The migration ability and invasiveness of cells were increased.These results indicated that alpha particles can induce EMT in Beas-2B cells.(2)When Beas-2B cells were treated with TNF-α,they exhibited morphology and EMT marker proteins expression alteration as those irradiated by α particles,suggesting that TNF-α can induce EMT in Beas-2B cells as well.(3)When Beas-2B cells were co-treated with α-particles and TNF-α,a more pronounced spindle-like stromal cell morphology were observed.Migration ability and invasiveness of cells were increased more significantly than α-particles or TNF-α treatment alone.On the other hand,when cells were treated with irradiation and TNF-α neutralizing antibody,cell morphology,migration ability and invasiveness were comparable to those of un-treated control.Our results suggested that TNF-α may be involved in the EMT process induced by alpha-irradiation.When the activity of TNF-α was suppressed by neutralizing antibody,EMT was blocked.Further studies will be needed to understand the pathways involved in such a process.