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Long-Term Cultured Human Glioblastoma Multiforme Cells Demonstrate Increased Radiosensitivity and Senescence- Associated Secretory Phenotype in Response to Irradiationстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Alhaddad Lina, Nofal Zain, Pustovalova Margarita, Osipov Andreyan N., Leonov Sergey
- Журнал: International Journal of Molecular Sciences
- Год издания: 2023
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Аннотация: The overall effect of senescence on cancer progression and cancer cell resistance to X-ray radiation (IR) is still not fully understood and remains controversial. How to induce tumorcell senescence and which senescent cell characteristics will ensure the safest therapeutic strategyfor cancer treatment are under extensive investigation. While the evidence for passage number-related effects on malignant primary cells or cell lines is compelling, much less is known about howthe changes affect safety and Senescence-Associated Secretory Phenotype (SASP), both of whichare needed for the senescence cell-based vaccine to be effective against cancer. The present studyaimed to investigate the effects of repeated passaging on the biological (self-renewal capacity andradioresistance) and functional (senescence) characteristics of the different populations of short-and long-term passaging glioblastoma multiforme (GBM) cells responding to senescence-inducingDNA-damaging IR stress. For this purpose, we compared radiobiological effects of X-ray exposureon two isogenic human U87 cell lines: U87L, minimally cultured cells (<15 passages after obtainingfrom the ATCC) and U87H, long-term cultured cells (>3 years of continuous culturing after obtainingfrom the ATCC). U87L cells displayed IR dose-related changes in the signs of IR stress-inducedpremature senescence. These included an increase in the proportion of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, and concomitant decrease in the proportion of Ki67-positivecells and metabolically active cells. However, reproductive survival of irradiated short-term culturedU87L cells was higher compared to long-term cultured U87H cells, as the clonogenic activity resultsdemonstrated. In contrast, the irradiated long-term cultured U87H cells possessed dose-relatedincreases in the proportion of multinucleated giant cancer cells (MGCCs), while demonstrating higherradiosensitivity (lower self-renewal) and a significantly reduced fraction of DNA-replicating cellscompared to short-term cultured U87L cells. Conditioned culture medium from U87H cells induceda significant rise of SA-β-Gal staining in U87L cells in a paracrine manner suggesting inherent SASP.Our data suggested that low-dose irradiated long-term cultured GBM cells might be a safer candidatefor a recently proposed senescence cell-based vaccine against cancer
- Добавил в систему: Алхаддад Лина