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Distinct phenotypes and ´bystander' effects of senescent tumour cells induced by docetaxel or immunomodulatory cytokines
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SYSNO ASEP 0502293 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Distinct phenotypes and ´bystander' effects of senescent tumour cells induced by docetaxel or immunomodulatory cytokines Author(s) Sapega, Olena (UMG-J)
Mikyšková, Romana (UMG-J) RID
Bieblová, Jana (UMG-J)
Mrázková, Blanka (UMG-J)
Hodný, Zdeněk (UMG-J) RID
Reiniš, Milan (UMG-J) RIDNumber of authors 6 Source Title International Journal of Oncology. - : Spandidos Publications - ISSN 1019-6439
Roč. 53, č. 5 (2018), s. 1997-2009Number of pages 13 s. Language eng - English Country GR - Greece Keywords cellular senescence ; ´bystander' senescence ; docetaxel ; immunostimulatory cytokines ; tumour microenvironment Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GA15-24769S GA ČR - Czech Science Foundation (CSF) GA15-03379S GA ČR - Czech Science Foundation (CSF) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000447703300014 DOI 10.3892/ijo.2018.4553 Annotation Cellular senescence is the process of the permanent proliferative arrest of cells in response to various inducers. It is accompanied by typical morphological changes, in addition to the secretion of bioactive molecules, including proinflammatory cytokines and chemokines [known as the senescence-associated secretory phenotype (SASP)]. Thus, senescent cells may affect their local environment and induce a so-called bystander' senescence through the state of SASP. The phenotypes of senescent cells are determined by the type of agent inducing cellular stress and the cell lineages. To characterise the phenotypes of senescent cancer cells, two murine cell lines were employed in the present study: TC-1 and B16F10 (B16) cells. Two distinct senescence inductors were used: Chemotherapeutic agent docetaxel (DTX) and a combination of immunomodulatory cytokines, including interferon (IFN) and tumour necrosis factor (TNF). It was demonstrated that DTX induced senescence in TC-1 and B16 tumour cell lines, which was demonstrated by growth arrest, positivegalactosidase staining, increased p21(Waf1) (p21) expression and the typical SASP capable of inducing a bystander' senescence. By contrast, treatment with a combination of T helper cell 1 cytokines, IFN and TNF, induced proliferation arrest only in B16 cells. Despite the presence of certain characteristic features resembling senescent cells (proliferation arrest, morphological changes and increased p21 expression), these cells were able to form tumours in vivo and started to proliferate upon cytokine withdrawal. In addition, B16 cells were not able to induce a bystander' senescence. In summary, the present study described cell line- and treatment- associated differences in the phenotypes of senescent cells that may be relevant in optimization of cancer chemo- and immunotherapy. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2019
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