Post-Irradiated Tumor-Derived Exosomes Lead to Melanoma Tumor Growth Delay, Potentially Mediated by Death Associated Molecular Pattern (DAMPs) Proteins

Jella, Kishore Kumar; Nasti, Tahseen H.; Li, Z.; Lawson, David H.; Ahmed, Rebaz; Dynan, William S.; Khan, Mdrakibhasan

doi:10.1016/j.ijrobp.2018.06.374

Cited by 5 publications

(5 citation statements)

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“…In this regard, Takahashi and co-workers demonstrated that exosome secretion contributes to maintain cell homeostasis by eliminating DNA fragments from cell cytoplasm [43]. Moreover, recent evidence has revealed that exosomes from radiated cells could modify target cell function [44], whereas the IR can alter cargo of exosomes [45]. As previous studies have shown that exosomes from stressed cells induce the stress in unstressed cells, the so-called bystander effect [46].…”

Section: Discussionmentioning

confidence: 99%

Ionizing Radiation Increases the Activity of Exosomal Secretory Pathway in MCF-7 Human Breast Cancer Cells: A Possible Way to Communicate Resistance against Radiotherapy

Jabbari

Nawaz

Rezaie

2019

IJMS

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Radiation therapy, which applies high-energy rays, to eradicate tumor cells, is considered an essential therapy for the patients with breast cancer. Most tumor cells secrete exosomes, which are involved in cell-to-cell communication in tumor tissue and contribute therapeutic resistance and promote tumor aggressiveness. Here, we investigated the effect of clinically applicable doses of X-ray irradiation (2, 4, 6, 8, 10 Gy) on the dynamics of the exosomes’ activity in MCF-7 breast cancer cells. Survival and apoptosis rate of cells against X-ray doses was examined using MTT and flow cytometry assays, respectively. Whereas, the levels of reactive oxygen species (ROS) in the X-ray-treated cells were detected by fluorometric method. The mRNA levels of vital genes involved in exosome biogenesis and secretion including Alix, Rab11, Rab27a, Rab27b, TSPA8, and CD63 were measured by real-time PCR. The protein level of CD63 was examined by Western blotting. Additionally, exosomes were characterized by monitoring acetylcholinesterase activity, transmission electron microscopy, size determination, and zeta potential. The result showed that in comparison with control group cell survival and the percentage of apoptotic cells as well as amount of ROS dose-dependently decreased and increased in irradiated cells respectively (p < 0.05). The expression level of genes including Alix, Rab27a, Rab27b, TSPA8, and CD63 as well as the protein level of CD63 upraised according to an increase in X-ray dose (p < 0.05). We found that concurrent with an increasing dose of X-ray, the acetylcholinesterase activity, size, and zeta-potential values of exosomes from irradiated cells increased (p < 0.05). Data suggest X-ray could activate exosome biogenesis and secretion in MCF-7 cells in a dose-dependent way, suggesting the therapeutic response of cells via ROS and exosome activity.

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Section: Discussionmentioning

confidence: 99%

Ionizing Radiation Increases the Activity of Exosomal Secretory Pathway in MCF-7 Human Breast Cancer Cells: A Possible Way to Communicate Resistance against Radiotherapy

Jabbari

Nawaz

Rezaie

2019

IJMS

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“…Damage-associated molecular pattern proteins (DAMPs) within CDEXs have also been heavily implicated. HSP70, HMGB1, and calreticulin are examples of proteins demonstrated to be upregulated within CDEXs following in vitro irradiation of melanoma, glioblastoma, and prostate cancer cell lines (101,108,109). In general, this group of proteins stimulates immune function via the innate system (both DCs and NKs), which has been demonstrated experimentally.…”

Section: Radiation Therapymentioning

confidence: 91%

Section: Therapeutic Implicationsmentioning

confidence: 99%

“…Jella et al have demonstrated the presence of multiple DAMPs in murine melanoma-derived CDEXs, which were induced by in vitro irradiation of tumor cells ( 109 ). Isolation and then co-culture of these CDEXs with naïve DCs resulted in preferential uptake and activation of DCs ( 109 ). Knock-out studies have also shown the importance of these proteins in anti-cancer immune effects following cytotoxic treatments ( 110 , 111 ).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

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A Clinician's Guide to Cancer-Derived Exosomes: Immune Interactions and Therapeutic Implications

Knox

Bece

et al. 2020

Front. Immunol.

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Understanding of the role of immunity in the regulation of cancer growth continues to rapidly increase. This is fuelled by the impressive results yielded in recent years by immune checkpoint inhibitors, which block regulatory pathways to increase immune-mediated cancer destruction. Exosomes are cell-secreted membranous nanoscale vesicles that play important roles in regulating physiological and pathophysiological processes. Cancer-derived exosomes (CDEXs) and their biologically-active cargos have been proven to have varied effects in malignant progression, including the promotion of angiogenesis, metastasis, and favorable microenvironment modification. More recently, there is an increasing appreciation of their role in immune evasion. In addition to CDEXs, there are immune-derived exosomes that facilitate communication between immune cells in the non-malignant setting. Investigation of cancer-mediated mechanisms behind interruption or modification of these normal exosomal pathways may provide further understanding of how malignant immune evasion is accomplished. Accumulating evidence indicates that immune-active CDEXs also have the potential to impact clinical oncological management. Whilst immune checkpoint inhibitors have well-established pharmacologically-targeted pathways involving the immune system, other widely used treatments such as radiation and cytotoxic chemotherapies do not. Thus, investigating exosomes in immunotherapy is important for the development of next-generation combination therapies. In this article, we review the ways in which CDEXs impact individual immune cell types and how this contributes to the development of immune evasion. We discuss the relevance of lymphocytes and myeloid-lineage cells in the control of malignancy. In addition, we highlight the ways that CDEXs and their immune effects can impact current cancer therapies and the resulting clinical implications.

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“…The radiated tumor cells secrete exosomal cargo to mediate cell-to-cell communication during radiation therapy, and consequently acquire therapeutic resistance to IR irradiation [ 84 ]. In addition, the exosomes from stressed and radiated cells could modify adjacent cell function and enhance the bystander effect, i.e., stemness on the adjacent cells to become more radioresistant and foster tumor aggressiveness [ 4 , 85 ]. For instance, the irradiation of MCF-7 cells in vitro with X-rays significantly conferred exosome biogenesis and radioresistance in a dose-dependent manner [ 84 ].…”

Section: Exosomes and Stemnessmentioning

confidence: 99%

The Role of Exosomes in Stemness and Neurodegenerative Diseases—Chemoresistant-Cancer Therapeutics and Phytochemicals

Beeraka

Doreswamy

Sadhu

et al. 2020

IJMS

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Exosomes exhibit a wide range of biological properties and functions in the living organisms. They are nanometric vehicles and used for delivering drugs, as they are biocompatible and minimally immunogenic. Exosomal secretions derived from cancer cells contribute to metastasis, immortality, angiogenesis, tissue invasion, stemness and chemo/radio-resistance. Exosome-derived microRNAs (miRNAs) and long non-coding RNAs (lnc RNAs) are involved in the pathophysiology of cancers and neurodegenerative diseases. For instance, exosomes derived from mesenchymal stromal cells, astrocytes, macrophages, and acute myeloid leukemia (AML) cells are involved in the cancer progression and stemness as they induce chemotherapeutic drug resistance in several cancer cells. This review covered the recent research advances in understanding the role of exosomes in cancer progression, metastasis, angiogenesis, stemness and drug resistance by illustrating the modulatory effects of exosomal cargo (ex. miRNA, lncRNAs, etc.) on cell signaling pathways involved in cancer progression and cancer stem cell growth and development. Recent reports have implicated exosomes even in the treatment of several cancers. For instance, exosomes-loaded with novel anti-cancer drugs such as phytochemicals, tumor-targeting proteins, anticancer peptides, nucleic acids are known to interfere with drug resistance pathways in several cancer cell lines. In addition, this review depicted the need to develop exosome-based novel diagnostic biomarkers for early detection of cancers and neurodegenerative disease. Furthermore, the role of exosomes in stroke and oxidative stress-mediated neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) is also discussed in this article.

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Post-Irradiated Tumor-Derived Exosomes Lead to Melanoma Tumor Growth Delay, Potentially Mediated by Death Associated Molecular Pattern (DAMPs) Proteins

Cited by 5 publications

References 0 publications

Ionizing Radiation Increases the Activity of Exosomal Secretory Pathway in MCF-7 Human Breast Cancer Cells: A Possible Way to Communicate Resistance against Radiotherapy

Ionizing Radiation Increases the Activity of Exosomal Secretory Pathway in MCF-7 Human Breast Cancer Cells: A Possible Way to Communicate Resistance against Radiotherapy

A Clinician's Guide to Cancer-Derived Exosomes: Immune Interactions and Therapeutic Implications

The Role of Exosomes in Stemness and Neurodegenerative Diseases—Chemoresistant-Cancer Therapeutics and Phytochemicals

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