Mushtaq Muhammad, Pangigadde Pradeepa N, Darekar Suhas, Dissen Erik, Kashuba Elena
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
University "Magna Græcia" of Catanzaro, Viale Europa, Catanzaro, Italy.
Oncotarget. 2017 May 4;8(39):64907-64917. doi: 10.18632/oncotarget.17610. eCollection 2017 Sep 12.
Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX family proteins were up-regulated significantly. It is known that the COX family proteins are involved in the regulation of immune response. In the present work we demonstrate that 18IM cells behave like stem cells when subjected to directed differentiation . However, unlike stem cells, 18IM cells do not develop tumors , in SCID mice. This phenomenon is observed due to the strong natural killer (NK) cell immunogenicity. 18IM cells were better recognized by NK cells, compared with primary REFs, as was shown by a standard NK killing assay. Our data explain asymmetry in behavior of stem-like cells and , and this support the notion that stem and/or cancer-initiating cells are preferred targets for NK-cells. Concluding, the S18-2 protein is a putative target for cancer vaccines.
人线粒体核糖体蛋白MRPS18 - 2（S18 - 2）的过表达导致原代大鼠胚胎成纤维细胞（REFs）永生化。衍生细胞（18IM）表达胚胎干细胞标志物。值得注意的是，编码COX家族蛋白的基因显著上调。已知COX家族蛋白参与免疫反应的调节。在本研究中，我们证明18IM细胞在定向分化时表现得像干细胞。然而，与干细胞不同，18IM细胞在SCID小鼠中不会形成肿瘤。由于强大的自然杀伤（NK）细胞免疫原性，观察到了这种现象。如标准NK杀伤试验所示，与原代REFs相比，18IM细胞更容易被NK细胞识别。我们的数据解释了干细胞样细胞行为的不对称性，这支持了干细胞和/或癌症起始细胞是NK细胞首选靶标的观点。总之，S18 - 2蛋白是癌症疫苗的一个假定靶点。
