Ionizing radiation-induced cellular senescence promotes tissue fibrosis after radiotherapy. A review

Nguyen, Hoang Q.; To, Nhu Hanh; Zadigue, Patricia; Kerbrat, Stéphane; Taille, Alexandre de la; Gouvello, Sabine Le; Belkacémi, Yazid

doi:10.1016/j.critrevonc.2018.06.012

Cited by 70 publications

(51 citation statements)

References 106 publications

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“…In a subset of tumours such as haematopoietic malignancies (Radford et al, 1994;Jonathan et al, 1999), radiation results in immediate interphase apoptosis. In the majority of solid tumours however, mitotic catastrophe is the most frequent context of radiation-induced cell death (Eriksson and Stigbrand, 2010), whereas normal tissues commonly undergo senescence after irradiation (Nguyen et al, 2018).…”

Section: Cell-intrinsic Factorsmentioning

confidence: 99%

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Sia

Szmyd

Hau

et al. 2020

Front. Cell Dev. Biol.

251

184

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Radiation therapy (RT) is responsible for at least 40% of cancer cures, however treatment resistance remains a clinical problem. There have been recent advances in understanding the molecular mechanisms of radiation-induced cell death. The type of cell death after radiation depends on a number of factors including cell type, radiation dose and quality, oxygen tension, TP53 status, DNA repair capacity, cell cycle phase at time of radiation exposure, and the microenvironment. Mitotic catastrophe (a pathway preceding cell death that happens in mitosis or as a consequence of aberrant mitotic progression) is the primary context of radiation-induced cell death in solid cancers, although in a small subset of cancers such as haematopoietic malignancies, radiation results in immediate interphase apoptosis, occurring within hours after exposure. There is intense therapeutic interest in using stereotactic ablative body radiotherapy (SABR), a precise, high-dose form of RT given in a small number of fractions, to prime the immune system for cancer cell killing, but the optimal radiation dose and fractionation remain unclear. Additionally, promising novel radiosensitisers targeting the cell cycle and DNA repair pathways are being trialled. In the context of the increasing use of SABR and such novel agents in the clinic, we provide an updated primer on the major types of radiation-induced cell death, focussing on their molecular mechanisms, factors affecting their initiation, and their implications on immunogenicity.

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Section: Cell-intrinsic Factorsmentioning

confidence: 99%

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Sia

Szmyd

Hau

et al. 2020

Front. Cell Dev. Biol.

251

184

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“…BMSCs were complicated during their whole lifespan, our In vitro cell-based assays showed that Bleomycin wouldn't lead to signi cant change in their cell cycle and apoptosis rate in a short-term use, which preserved the possibility of future clinical usage. Moreover, The short-term Bleomycin could induce BMSCs towards a stronger broblast phenotype, although with long-term usage it might cause the cells undergone aging (In some studies the senescence of BMSCs or other cells were found to be associated with the transition into brotic phenotype [39,40]), and for broblastic-like cell AF cells it could promote the migration and Collagen deposition via TGFβ-TGFβR1-SMAD2/3 signaling pathway. Bleomycin could upregulate the MMP3 and MMP13 to remodel the ECM (Suppl.…”

Section: Discussionmentioning

confidence: 99%

Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGFβR1/Smad2/3 pathway

Xiao¹,

chen²,

Chen³

et al. 2020

Preprint

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Background: Lower back pain is often accredited to loss of intervertebral disc (IVD) height and compromised spine stability as a result of intervertebral disc degeneration (IVDD). We aim to locally use Bleomycin to induce the fibrotic transformation of bone marrow stromal cells (BMSCs) as a means to induce reparative fibrosis to slow down the height loss. Methods: IVD from patients were gathered for histological examination. The expression of transforming growth factor beta 1 (TGF-β) signaling pathway was determined by qPCR and western blotting. Nucleus pulposus (NP) cells, annulus fibrosus (AF) cells and the Rats’ bone marrow stromal cells (BMSC)were cultured and their responsiveness to Bleomycin was evaluated by Cell Counting Kit-8, comet assay, transwell migration and wound healing assays. Rat IVDD models were created by puncture, rescued by Bleomycin injection and the effectiveness was evaluated by images (X-ray and MRI) and atomic force microscope. Results: Histological examination showed increased levels of pro-fibrotic markers in IVDD tissues from patients. AF cells and BMSC cells was induced to adopt to a pro-fibrotic phenotype with increased expression fibrotic markers Col1a1, Col3a1, FSP1. The pro-fibrotic effect of Bleomycin on AF cells and BMSCs was in part due to the activation of the TGFβ-TGFβR1-SMAD2/3 signaling pathway. Pharmacological inhibition or gene knock-down of TGFβR1 could mitigate the pro-fibrotic effects. Conclusion: Locally injection of Bleomycin in rats’ IVD induced rapid fibrosis and maintained its height through TGFβ-TGFβR1-SMAD2/3 signaling pathway.

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“…In the senescence process induced by IR, the cell cycle is interrupted by G2 arrest after inevitable DNA damage, accompanied by mitotic bypass into the G1 phase (16). Ataxia telangiectasia-mutated protein (ATM), p53, p21, p16-Rb, p38-mitogen-activated protein kinase (p38-MAPK), NF-κB signalling pathway factors, reactive oxygen species (ROS), senescence-associated secretory phenotype (SASP) factors and cyclin-CDK complexes are involved in this process (9,16,17). Different doses of IR and DNA damage can lead to various types of cells with mitotic cell cycle delays, including arrests in the G1, G2 or S phase.…”

Section: Ir-induced Csmentioning

confidence: 99%

“…Many radiosensitizers are aimed at increasing CS when combined with IR (7,8). On the other hand, IR can induce senescence in surrounding and normal cells as well as in cancer cells, which leads to normal tissue fibrosis and organ dysfunction (9). Moreover, IR-induced CS (IRIS) may emerge as a method for helping cancer cells overcome RT and worsen the biological behaviour of tumour cells following IR treatment (10,11).…”

Section: Introductionmentioning

confidence: 99%

Cellular senescence in ionizing radiation (Review)

et al. 2019

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Radiotherapy (RT) is one of most common treatments for cancer. However, overcoming the failure and side effects of RT as well as radioresistance, recurrence and metastasis remains challenging in cancer treatment. Cellular senescence (CS) is permanent arrested state of cell division induced by various factors, including exposure to ionizing radiation (IR). CS induced by IR contributes to tumour cell control and often even causes side effects in normal cells. Improvement of the therapeutic RT ratio is dependent on more cancer cell death and less normal cell damage. In addition, the biological behaviour of tumour cells after IR has also been linked to CS. This review summarizes our understanding of CS in IR, which may be beneficial for providing new insight for improving the therapeutic outcomes of RT. Contents 1. Introduction 2. IR-induced CS 3. CS and radiosensitivity 4. CS and IR side effects 5. IRIS and tumour cell biological behaviour 6. Other related mechanisms 7. Future perspectives

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Ionizing radiation-induced cellular senescence promotes tissue fibrosis after radiotherapy. A review

Cited by 70 publications

References 106 publications

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGFβR1/Smad2/3 pathway

Cellular senescence in ionizing radiation (Review)

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