The Function And The Preliminary Mechanism Discussion Of The Cell Adhesion Molecule Ninjurin-2 In The Human Glioblastoma Cell Lines U87-MG Etc.

Glioblastoma Multiforme(GBM)is the second common brain tumor in the world.Because of its unusual position in the brain and its special biochemical or physiological characteristics,and limited therapeutic methods,it can be barely cured nowadays.Our group used the human glioblastoma cell lines U87-MG etc.as the cellular models of the disease and then found that a novel small cell adhesion molecule Ninjurin-2 can play a special role in the cellular models.Ninjurin-2 is one of the cell adhesion molecules,but there are little reports about its function and mechanism.There were more researches about the other molecules in this family such as Ninjurin-1 and Ninjurin A,but they all didn't involve in tumor.Our group worked on this area and study the relationship between Ninjurin-2 and glioblastoma.We searched NINJ2 in the Oncomine database and found that the level of NINJ2 gene in the CNS tumor is lower,suggesting that NINJ2 may have the function of inhibition to this kind of tumors.Then we confirmed that over-expressed NINJ2 in the human glioblastoma cell lines U87-MG etc.can initiate the early stage of apoptosis and decrease the viability of these cells by using CCK-8 and flow cytometry analysis.At the same time,we found that NINJ2 have no influence on the cell migration and the distribution of cell cycle.Later,we used two tumor xenograft models to observe the influence of NINJ2 to the tumor formation and the results in vivo,which were consistent with the results in vitro,proving that Ninjurin-2 can decrease tumor formation.Finally we performed a preliminary mechanism study about such phenotypes and raised a hypothesis that Ninjurin-2 may cause the cellular stress reactions,and such reactions may go through the ER stress and mTOR pathways to initiate the early stage of apoptosis.However,this hypothesis need more experimental evidence to support it.The inhibition to the cellular growth and to the ability of the tumor forming in human glioblastoma cell lines U87-MG etc.caused by Ninjurin-2 protein may give us a cue that the mechanism working on the cellular models may also work on the GBM.Studies about the role of Ninjurin-2 in tumorigenesis might shed a light on GBM therapy in future.