Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors

Frontiers in Immunology
Jin ChenLuis E Muñoz

Abstract

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. 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 in vivo. The stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We...Continue Reading

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Citations

Oct 25, 2017·Frontiers in Immunology·Philippe SaasSylvain Perruche
May 10, 2020·Health Physics·Evagelia C LaiakisAlbert J Fornace
Apr 4, 2021·Biomolecules·Bundit PromraksaWatcharin Loilome
Jun 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lisa EhlersTimo Gaber
Sep 7, 2021·Frontiers in Oncology·Malgorzata J PodolskaLuis E Muñoz
Oct 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jianjun DengDipak Panigrahy

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Methods Mentioned

BETA
flow cytometry
size exclusion chromatography

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis