Prevanlance Of Heterotypic Tumor/Immune Cell-in-cell Involved In Inflammation, Cancer And Cell Infection

Cell-in-cell structure refers to a unique phenomenon that one living cell enters intoanother living cell intactly. Cell-in-cell structures can be divided into two basic types:heterotypic interactions, in which a cell is internalized into a host of a different celltype, and homotypic interactions, in which a cell is internalized into a host of the samecell type. The heterotypic cell-in-cell structures formed by lymphocytes into tumorcells or normal cells were discussed here in our study.In the present study, through a large scale of survey we observed that heterotypiccell-in-cell structure formation occurred commonly in vitro with host cells derivedfrom different human carcinomas as well as xenotypic mouse tumor cell lines. Mostof the lineages of human immune cells, including T, B, NK cells, monocytes as wellas in vitro activated LAK cells, were able to invade tumor cell lines. Poorlydifferentiated stem cells were capable of internalizing immune cells as well. Itsuggested that maybe cell-in-cell wass a very primitive phenomenon and played anextremely important role in the process of biological evolution.More significantly, heterotypic tumor/immune cell-in-cell structures were observedin a higher frequency in tumor-derived tissues than those in adjacent tissues afteranalysis on kinds of human carcinomas in vivo. In mouse hepatitis models,heterotypic immune cell/hepatocyte cell-in-cell structures were also formed in ahigher frequency than in normal controls. After in vitro culture, different forms ofinternalized immune cells in heterotypic cell-in-cell structures were observed, withone or multiple immune cells inside host cells undergoing resting, degradation ormitosis. More strikingly, some internalized immune cells penetrated directly into thenucleus of target cells.Multinuclear cells with aneuploid nucleus were formed in target tumor cells afterinternalizing immune cells as well as in situ tumor regions. Therefore, with theprevalence of heterotypic cell-in-cell structures observed, we suggest that shielding ofimmune cells inside tumor or inflammatory tissue cells implies the formation ofaneuploidy with the increased multinucleation as well as fine-tuning ofmicroenvironment under pathological status, which may define distinct mechanisms to influence the etiology and progress of tumors.The spread of virus between cells, tissues, persons or even spices contributed to thepersistent infection. Each kind of virus has its own preferred host cells with specialreceptor such as, EBV virus usually infected CD21+cells and HIV virus infected CD4+cells. The mechanism that the virus infected non receptor cells was unknown. Thesuccessful infection was achieved by cell-in-cell formed by culturing recombinantEBV (Akata strain) carrying a selective marker gene but without any other artificialoperations with three CD21human epithelial cell lines examined as ascertained by thedetection of EBV-determined nuclear antigen (EBNA)1expression in the early periodafter virus exposure. This novel intracellular infection mechanism was furtherconfirmed by the culture H9/IIIB cells with CD4negative human epithelial cells. Theheterotypic cell-in-cell structures formed by EBV positive Akata cells and CNE-2cells were sorted by FACS and selected by G418medium after7days culture. Thesorted CNE-2cells were successfully infected by EBV indicated by GFP andconfirmed by immunofluorescence and TEM. The EBV gene was proved to integratedinto the nuclear of sorted CNE-2cells resulting with the persist infection of CNE-2cells. Interestingly, the virus asmbled and released by sorted CNE-2can be infectiousto many kinds of cells including lymphocytes and epithelial cells. The infectiousCNE-2cells by cell-in-cell infection maybe changes a lot in biological characteristics,the expression of viral antigens, the synthetic of virus, the chromosomal instabilityand can easily be induced to neoplastic (tumorigenic) cell and work as a freshmanvirus source which continue to infect neighbour cell by cell free infection orcell-to-cell infection followed by the formation of infection island.