Rat embryonic fibroblasts immortalized by MRPS18-2 protein are target for NK-cells

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.

The MRPS18-2 protein levels correlate with prostate tumor progression and it induces CXCR4-dependent migration of cancer cells

“…Another possible reason of smaller tumor size of S18-2 overexpressing cells might be due to the fact that overexpression of S18-2 induce NK cells mediated cytotoxicity. We have shown such asymmetric behavior of S18-2 overexpressing rat embryonic fibroblast both, in vivo and in vitro 26 .…”