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Chen J, Chaurio RA, Maueröder C, et al. Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation . Front Immunol. 2017;8:504doi: 10.3389/fimmu.2017.00504.
Chen, J., Chaurio, R. A., Maueröder, C., Derer, A., Rauh, M., Kost, A., Liu, Y., Mo, X., Hueber, A., Bilyy, R., Herrmann, M., Zhao, Y., & Muñoz, L. E. (2017). Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation . Frontiers in immunology, 8504. https://doi.org/10.3389/fimmu.2017.00504
Chen, Jin, et al. "Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation ." Frontiers in immunology vol. 8 (2017): 504. doi: https://doi.org/10.3389/fimmu.2017.00504
Chen J, Chaurio RA, Maueröder C, Derer A, Rauh M, Kost A, Liu Y, Mo X, Hueber A, Bilyy R, Herrmann M, Zhao Y, Muñoz LE. Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation . Front Immunol. 2017 Apr 27;8:504. doi: 10.3389/fimmu.2017.00504. eCollection 2017. PMID: 28496447; PMCID: PMC5406388.
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Front Immunol. 2017 Apr 27;8:504. doi: 10.3389/fimmu.2017.00504. eCollection 2017.

Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation .

Frontiers in immunology

Jin Chen, Ricardo A Chaurio, Christian Maueröder, Anja Derer, Manfred Rauh, Andriy Kost, Yi Liu, Xianming Mo, Axel Hueber, Rostyslav Bilyy, Martin Herrmann, Yi Zhao, Luis E Muñoz

Affiliations

  1. Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.
  2. Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany.
  3. Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany.
  4. Kinder- und Jugendklinik, Universitätsklinikum Erlangen, Erlangen, Germany.
  5. Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
  6. Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.

PMID: 28496447 PMCID: PMC5406388 DOI: 10.3389/fimmu.2017.00504

Abstract

INTRODUCTION: Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells.

METHODS: Cultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS) in the presence of dead and dying cells, their supernatants (SNs), or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth

RESULTS: The stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting

CONCLUSION: Inosine released by dead and dying cells mediates tumor cell proliferation

Keywords: adenosine receptor; apoptosis; inosine; melanoma; necrosis; proliferation; repopulation

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