The Dual Role of Senescence in Tumorigenesis

Chuaire-Noack, Lilian; Sánchez-Corredor, Magda Carolina; Ramírez-Clavijo, Sandra

doi:10.4067/s0717-95022010000100006

Cited by 9 publications

(7 citation statements)

References 85 publications

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“…Our analyses indicated a considerable diversity both, in the presence and percentage of senescent cells – cells positive for SA-β-Gal activity were detected within T98G, U87-MG and DK-MG lines, with the last line characterized by the highest percentage of senescent cells. These results may support the theory of dual – anti- and pro-neoplastic role of senescence [39], complicating manipulations of this phenomenon in anticancer research as well as unequivocal understanding of the mechanism of this process and its implications. Finally, not only idiopathic senescence, but also idiopathic/spontaneous apoptosis was observed in primary and stabilized GB cell lines.…”

Section: Discussionsupporting

confidence: 65%

A way to understand idiopathic senescence and apoptosis in primary glioblastoma cells – possible approaches to circumvent these phenomena

et al. 2019

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Background Glioblastoma (GB) is considered one of the most lethal tumors. Extensive research at the molecular level may enable to gain more profound insight into its biology and thus, facilitate development and testing of new therapeutic approaches. Unfortunately, stable glioblastoma cell lines do not reflect highly heterogeneous nature of this tumor, while its primary cultures are difficult to maintain in vitro. We previously reported that senescence is one of the major mechanisms responsible for primary GB cells stabilization failure, to a lesser extent accompanied by apoptosis and mitotic catastrophe-related cell death. Methods We made an attempt to circumvent difficulties with glioblastoma primary cultures by testing 3 different approaches aimed to prolong their in vitro maintenance, on a model of 10 patient-derived tumor specimens. Results Two out of ten analyzed GB specimens were successfully stabilized, regardless of culture approach applied. Importantly, cells transduced with immortalizing factors or cultured in neural stem cell-like conditions were still undergoing senescence/apoptosis. Sequential in vivo/in vitro cultivation turned out to be the most effective, however, it only enabled to propagate cells with preserved molecular profile up to 3rd mice transfer. Nevertheless, it was the only method that impeded these phenomena long enough to provide sufficient amount of material for in vitro/in vivo targeted analyses. Interestingly, our data additionally demonstrated that some subpopulations of several stabilized GB cell lines undergo idiopathic senescence, however, it is counterbalanced by simultaneous proliferation of other cell subpopulations. Conclusions In the majority of primary glioma cultures, there has to be an imbalance towards apoptosis and senescence, following few weeks of rapid proliferation. Our results indicate that it has to be associated with the mechanisms other than maintenance of glioblastoma stem cells or dependence on proteins controlling cell cycle.

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Section: Discussionsupporting

confidence: 65%

A way to understand idiopathic senescence and apoptosis in primary glioblastoma cells – possible approaches to circumvent these phenomena

et al. 2019

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“…Generally, upon encounter with oncogenic stimuli which induce uncontrolled proliferation of cells, tumour suppressor markers such as p53 , p21 and p16 will be highly expressed, which in turn activates their downstream target, pRb . Upregulation of these tumour suppressor markers maintains pRb in its hypophosphorylated state, which results in cell cycle arrest and apoptosis to reduce cell proliferation, thus preventing the formation of tumours (Chuaire‐Noack et al ., ; Pelicci, ).…”

Section: Resultsmentioning

confidence: 99%

Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells

Yong

Safwani

et al. 2016

J Tissue Eng Regen Med

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Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of the tumour suppressor markers p53, p21, p16 and pRb, hTERT, telomerase activity and telomere length. Further, we did not observe significant DNA damage or signs of p53 mutation in cryopreserved hASCs. Our findings suggest that long-term cryopreserved hASCs are at low risk of tumourigenesis. These findings aid in establishing the biosafety profile of cryopreserved hASCs, and thus establishing low hazardous risk perception with the use of long-term cryopreserved hASCs for future clinical applications. Copyright © 2016 John Wiley & Sons, Ltd.

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“…36 The cells display several features which distinguish them from quiescent cells reversibly arrested in the G 1 phase of the cell cycle. 34,37 In particular, senescent cells adopt (1 morphological changes, i.e., they become larger and flattened and display an increased granularity, (2) changes in nuclear architecture characterized by of microtubules and spindle stability. [17][18][19][20] TACC3 is predominantly expressed during the G 2 /M phase of the cell cycle where it localizes in an Aurora-A phosphorylation and clathrin heavy chain-dependent manner to centrosomes and mitotic spindles ( Fig.…”

Section: Cellular Senescence-causes and Characteristicsmentioning

confidence: 99%

The centrosome and mitotic spindle apparatus in cancer and senescence

et al. 2010

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Altered cell division is associated with overproliferation and tumorigenesis, however, mitotic aberrations can also trigger antiproliferative responses leading to postmitotic cell cycle exit. Here, we focus on the role of the centrosome and in particular of centrosomal TACC (transforming acidic coiled coil) proteins in tumorigenesis and cellular senescence. We have complied recent evidence that inhibition or depletion of various mitotic proteins which take over key in centrosome and kinetochore integrity and mitotic checkpoint function in sufficient to activate a p53-p21(WAF) driven premature senescence phenotype. These findings have direct implications for proliferative tissue homeostasis as well as for cellular and organismal aging.

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The Dual Role of Senescence in Tumorigenesis

Cited by 9 publications

References 85 publications

A way to understand idiopathic senescence and apoptosis in primary glioblastoma cells – possible approaches to circumvent these phenomena

A way to understand idiopathic senescence and apoptosis in primary glioblastoma cells – possible approaches to circumvent these phenomena

Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells

The centrosome and mitotic spindle apparatus in cancer and senescence

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