Exosomes in Cancer Radioresistance

Ni, Jie; Bucci, Joseph; Malouf, David; Knox, Matthew C.; Graham, Peter; Li, Y.

doi:10.3389/fonc.2019.00869

Cited by 68 publications

(57 citation statements)

References 70 publications

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“…While cancer therapies adversely impact cognition, they also affect exosome biogenesis and release causing changes to the anatomy of the brain [104]. Cancer therapies also cause cellular stress that affect the release and composition of exosomes, thereby impacting neighboring and distant cells (e.g., brain) [108]. Moreover, radio-and chemotherapy may also influence the development of treatment-resistant cancer cells [75], possibly through cellular reprogramming [109] and/or the formation of brain metastasis [110].…”

Section: Mechanisms Associated With Exosomes and Crcimentioning

confidence: 99%

Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment.Int. J. Mol. Sci. 2020, 21, 2755 2 of 16 attention, learning, and executive function [10]. CRCI adversely affects cancer patients and survivors, causing distress and reduced quality of life, and impacts many facets of their daily lives [11]. CRCI is complicated by many factors including the direct effects of cancer, genetic predisposition (e.g., carrier of apolipoprotein E type epsilon 4 allele [12] and brain-derived neurotrophic factor Met allele [13]), comorbidities independent of the actual disease, and/or treatments or combinations of treatments administered for the disease [14].Efforts to better understand cancer-and cancer-therapy-associated cognitive impairment have relied on methods ranging from cognitive functioning assessment to imaging technologies on brain structure and function (e.g., magnetic resonance imaging scan). However, these approaches may be limited to help us understand the etiology and pathophysiology of cognitive dysfunction. The emerging application of the use of liquid biopsies (e.g., plasma and cerebrospinal fluid) as a strategy for biomarker discovery to detect, assess and monitor CRCI is fast-expanding and evolving [15,16]. In published literature, studies have revealed that genetics and neurobiological and immunological mechanisms may be involved in the biogenesis and development of CRCI. Preclinical studies have also provided insights into the pathophysiological mechanisms underlying CRCI, including neurotoxicity and inflammatory factors, which were shown to be responsible for CRCI [17]. Nevertheless, the underlying mechanisms of CRCI have yet to be established. While the role of exosomes in cancer has been well-documented [18][19][20], the role of cancer exosomes and their ability ...

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Section: Mechanisms Associated With Exosomes and Crcimentioning

confidence: 99%

Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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“…Studies have shown that exosomes are closely related to tumor radiotherapy resistance. 22 The proteome content of exosome is affected by radiation in head-and-neck cancer cells. In turn, exosomes are able to modify the radiation response.…”

Section: Discussionmentioning

confidence: 99%

“…Gain‐functional and loss‐functional experiments revealed that overexpression of circMYC could promote cell proliferation and reduce radiosensitivity, while knockdown of circMYC‐inhibited cell proliferation and enhanced radiotherapy effect. Studies have shown that exosomes are closely related to tumor radiotherapy resistance 22 . The proteome content of exosome is affected by radiation in head‐and‐neck cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma

Luo

Liu

et al. 2020

Head & Neck

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Background: The relationship between circulating exosomal circular RNA (circRNA) and prognosis of patients with nasopharyngeal carcinoma (NPC) remain unknown. This study focused on the expression of exosomal circMYC and its relationship with the recurrence and prognosis of patients with NPC. Methods: The circulating exosomes were obtained from 210 patients with NPC. Quantitative polymerase chain reaction, 5-ethynyl-2 0-deoxyuridine (EdU) staining, colony formation, and bioinformatic analysis were performed. Results: Circulating exosomal circMYC was significantly increased in patients with NPC and was associated with tumor size, lymph node metastasis, TNM stage, survival rate, and disease recurrence. Gain-functional and lossfunctional experiments revealed that overexpression of circMYC promoted cell proliferation and reduce radiosensitivity, while knockdown of circMYC inhibited cell proliferation and enhanced radiotherapy. Conclusion: circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.

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“…Xu and co-workers have reported that X-ray irradiation increase exosomes biogenesis and secretion (46). In addition, several laboratories demonstrated that EVs from irradiated tumor cells promoted genomic instability and resistance in non-irradiated cell (47,48). In summary, through investigating irradiated MCF-7 cells with the different doses of electron beam affecting the viability, apoptosis, EVs release, expression of genes involved in apoptosis and stemness, and migration capacity, we shed light into cellular responses of MCF-7 against EBI (Fig.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Bystander Effects of Electron Beam Irradiation in Radiotherapy on MCF-7 Human Breast Cancer Cells

Feghhi

Rezaie

Mostafanezhad

et al. 2019

Preprint

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Background: The distinct direct and non-targeting effects of electron beam radiation on MCF-7 cells remain unclear. We aimed to investigate the effect of electron beam radiation and conditioned media of the irradiated MCF-7 cells on MCF-7 cells.Methods: The cell viability and apoptosis were assayed via MTT and flow cytometry analysis, respectively. Production of oxygen reactive species was evaluated by chemical fluorometric method, while the amount of extracellular vesicles was detected via acetylcholinesterase activity assay. Change in the expression of genes involved in apoptosis including caspase-3, caspase-8, and caspase-9 and stemness such as Sox-2 and Oct-4 were calculated through qPCR. Wound healing rate of cells was monitored via in vitro scratch assy. Results: Result showed that compared to control group, electron beam radiation decreased cell viability and increased apoptosis and oxygen reactive species as well as acetylcholinesterase activity in a dose-dependent manner (P<0.05). Concurrent with increasing dose of electron beam, the mRNA level of apoptotic genes (caspase-3, caspase-8, and caspase-9) and stemness related genes (Sox-2 and Oct-4) up-regulated following electron beam radiation. Wound healing rate of irradiated MCF-7 cells dose-dependently increased (P<0.05). After treatment with conditioned media from irradiated MCF-7 cells, the similar results were observed. Conditioned media from irradiated MCF-7 cells decreased viability of MCF-7 cells, mesenchymal stem cells, and HUVECs (P<0.05). Additionally, conditioned media from irradiated MCF-7 cells promoted apoptosis and wound healing rate as well as increased mRNA levels of apoptosis and stemness related genes (P<0.05). Conclusion: Findings suggest electron beam radiation could affect apoptosis and stemness in MCF-7 cells in direct and bystander manners.

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Exosomes in Cancer Radioresistance

Cited by 68 publications

References 70 publications

Role of Exosomes in Cancer-Related Cognitive Impairment

Role of Exosomes in Cancer-Related Cognitive Impairment

Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma

Evaluating the Bystander Effects of Electron Beam Irradiation in Radiotherapy on MCF-7 Human Breast Cancer Cells

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