Research Papers:

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

Muhammad Mushtaq, Pradeepa N. Pangigadde, Suhas Darekar, Erik Dissen and Elena Kashuba _

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Oncotarget. 2017; 8:64907-64917. https://doi.org/10.18632/oncotarget.17610

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Muhammad Mushtaq1, Pradeepa N. Pangigadde1,2, Suhas Darekar1, Erik Dissen3 and Elena Kashuba1,4

1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

2 University “Magna Græcia” of Catanzaro, Viale Europa, Catanzaro, Italy

3 Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

4 R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Ukraine

Correspondence to:

Elena Kashuba, email:

Keywords: mitochondrial ribosomal protein MRPS18-2, cell immortalization, stem cells, NK killing, cytokine expression profile

Received: March 16, 2017 Accepted: April 24, 2017 Published: May 04, 2017


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.

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PII: 17610