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      Role of hypoxia-induced exosomes in tumor biology

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          Abstract

          Purpose

          Hypoxia is a major regulator of angiogenesis and always influences the release of exosomes in various types of tumors. The present review aimed to assess the role of hypoxia-induced exosomes in the tumor biology.

          Methods

          The relevant publications were retrieved from PubMed using keywords such as hypoxia, exosome, extracellular vesicles, tumor, cancer, and other similar terms.

          Results

          Recent studies have shown that cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. The secretion and function of exosomes could be influenced by hypoxia in various types of cancer. Hypoxia-induced exosomes play critical roles in tumor angiogenesis, invasion, metastasis, and the immune system.

          Conclusions

          These findings provide new insights into the complex networks underlying cellular and genomic regulation in response to hypoxia and might provide novel and specific targets for future therapies.

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          Most cited references44

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          HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

          M Ivan, K Kondo, H. Yang … (2001)
          HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.
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            Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes.

            Valentina R. Minciacchi, Michael R. Freeman, Dolores Di Vizio (2015)
            Since their first description, extracellular vesicles (EVs) have been the topic of avid study in a variety of physiologic contexts and are now thought to play an important role in cancer. The state of knowledge on biogenesis, molecular content and horizontal communication of diverse types of cancer EVs has expanded considerably in recent years. As a consequence, a plethora of information about EV composition and molecular function has emerged, along with the notion that cancer cells rely on these particles to invade tissues and propagate oncogenic signals at distance. The number of in vivo studies, designed to achieve a deeper understanding of the extent to which EV biology can be applied to clinically relevant settings, is rapidly growing. This review summarizes recent studies on cancer-derived EV functions, with an overview about biogenesis and molecular cargo of exosomes, microvesicles and large oncosomes. We also discuss current challenges and emerging technologies that might improve EV detection in various biological systems. Further studies on the functional role of EVs in specific steps of cancer formation and progression will expand our understanding of the diversity of paracrine signaling mechanisms in malignant growth.
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              Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response.

              S R McKeown (2014)
              Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.
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                Author and article information

                Contributors
                Chuchu Shao: s_chuchu@sina.com
                Fengming Yang: yfmdoctor@njmu.edu.cn
                Suyu Miao: 228354826@qq.com
                Weitao Liu: liuweitaoly@163.com
                Chaoshan Wang: 1274173060@qq.com
                Yongqian Shu: shuyongqian1998@163.com
                Hua Shen: medshenhua@126.com
                Journal
                Journal ID (nlm-ta): Mol Cancer
                Journal ID (iso-abbrev): Mol. Cancer
                Title: Molecular Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1476-4598
                Publication date (Electronic): 11 August 2018
                Publication date PMC-release: 11 August 2018
                Publication date Collection: 2018
                Volume: 17
                Electronic Location Identifier: 120
                Affiliations
                [1 ]ISNI 0000 0000 9255 8984, GRID grid.89957.3a, Department of Oncology, , The Affiliated Sir Run Run Hospital of Nanjing Medical University, ; Nanjing, China
                [2 ]ISNI 0000 0004 1799 0784, GRID grid.412676.0, Department of Oncology, , the First Affiliated Hospital of Nanjing Medical University, ; 300 Guangzhou Road, Nanjing, 210029 People’s Republic of China
                [3 ]ISNI 0000 0004 1799 0784, GRID grid.412676.0, Department of Breast Surgery, , The First Affiliated Hospital of Nanjing Medical University, ; Nanjing, China
                [4 ]ISNI 0000 0000 9255 8984, GRID grid.89957.3a, Department of Pathology, , Nanjing Medical University, ; Nanjing, China
                Article
                Publisher ID: 869
                DOI: 10.1186/s12943-018-0869-y
                PMC ID: 6087002
                PubMed ID: 30098600
                SO-VID: 858529ab-2cb0-4c4f-aee0-2f741ea95117
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 2 May 2018
                Date accepted : 1 August 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004608, Natural Science Foundation of Jiangsu Province;
                Award ID: No BK20171484
                Award Recipient :
                Funded by: Jiangsu Provincial Medical Youth Talent
                Award ID: QNRC2016856
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81672896
                Award Recipient :
                Funded by: Summit of the Six Top Talents Program of Jiangsu Province
                Award ID: 2017-WSN-179
                Award Recipient :
                Funded by: Practice Innovation Program of Jiangsu Province, and the Priority Academic Program Development of Jiangsu Higher Education Institutions
                Award ID: JX10231801
                Award Recipient :
                Funded by: Postgraduate Research & Practice Innovation Program of Jiangsu Province
                Award ID: KYCX18_1483
                Award Recipient :
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: exosome,extracellular vesicles,hypoxia,cancer
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: exosome, extracellular vesicles, hypoxia, cancer

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