Abstract
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 in vitro. However, unlike stem cells, 18IM cells do not develop tumors in vivo, 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 in vivo and in vitro, 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.
Highlights
The S18 family of mitochondrial ribosomal proteins (MRPS18, S18 in the text) consists of three proteins, S18-1-3 [1]
In the present work we demonstrate that 18IM cells behave like stem cells when subjected to directed differentiation in vitro
We have found that overexpression of the S182 protein (NP_054765) resulted in immortalization of primary rat embryonic fibroblasts (REFs), associated with induction of stem cell marker expression [2]
Summary
The S18 family of mitochondrial ribosomal proteins (MRPS18, S18 in the text) consists of three proteins, S18-1-3 [1]. We have found that overexpression of the S182 protein (NP_054765) resulted in immortalization of primary rat embryonic fibroblasts (REFs), associated with induction of stem cell marker expression [2]. It is known that COX and NDUF family proteins are involved in the control on cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions. This indicates that 18IM cells are more active metabolically than REFs. The cellular pathways characteristic for rapidly proliferating cells were activated in 18IM cells, namely the ubiquinone (Coenzyme Q10) biosynthesis, fatty acid elongation in mitochondria, and PI3K/AKT signaling [3]. A proportion of the cells started to express the beta-III-tubulin, MHC class II, and pan-keratin [2]
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