Distinct phenotypes and ´bystander' effects of senescent tumour cells induced by docetaxel or immunomodulatory cytokines

0502293 - ÚMG 2019 RIV GR eng J - Journal Article
Sapega, Olena - Mikyšková, Romana - Bieblová, Jana - Mrázková, Blanka - Hodný, Zdeněk - Reiniš, Milan
Distinct phenotypes and ´bystander' effects of senescent tumour cells induced by docetaxel or immunomodulatory cytokines.
International Journal of Oncology. Roč. 53, č. 5 (2018), s. 1997-2009. ISSN 1019-6439. E-ISSN 1791-2423
R&D Projects: GA ČR GA15-24769S; GA ČR GA15-03379S; GA MŠMT(CZ) LM2015040
Institutional support: RVO:68378050
Keywords : cellular senescence * ´bystander' senescence * docetaxel * immunostimulatory cytokines * tumour microenvironment
OECD category: Biochemistry and molecular biology
Impact factor: 3.571, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0294243