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      Extracellular heat shock proteins and cancer: New perspectives

      review-article
      Author(s): a , * , b , c , d , e , f , f , f
      Publication date (Electronic):
      Journal: Translational Oncology
      Publisher: Neoplasia Press
      Keywords: heat shock proteins, Extracellular vesicles, Extracellular HSPs, miRNA, Biomarker, cancer, HSP, heat shock proteins, miRNA, microRNA, MS, mass spectrometry, NSCLC, non-small cell lung cancer, AML, acute myeloid leukemia, ESCC, esophageal squamous cell carcinoma, CTC, circulating tumor cells, SCCNH, squamous cell carcinoma of the head and neck, GIST, gastrointestinal stromal tumor, HCC, hepatocellular carcinoma, DICS, ductal carcinoma in situ, CUSA, cavitron ultrasonic surgical aspirator, CHIP, C-terminus of HSP70 interacting protein, HOP, HSP70-HSP90 organizing protein, BAG, BCL2-associated athanogene, ccRCC, clear cell renal cell carcinoma, HL, Hodgkin lymphoma, DLBCL, Diffuse large B-cell lymphoma

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          Highlights

          • •

            High expression of extracellular heat shock proteins (HSPs) indicates highly aggressive tumors.

          • •

            HSP profiling of extracellular vesicles (EVs) derived from various biological fluids and released by immune cells may open new perspectives for an identification of diagnostic, prognostic and predictive biomarkers of cancer.

          • •

            Identification of specific microRNAs targeting HSPs in EVs may be a promising strategy for the discovery of novel biomarkers of cancer.

          Abstract

          Heat shock proteins (HSPs) are a large family of molecular chaperones aberrantly expressed in cancer. The expression of HSPs in tumor cells has been shown to be implicated in the regulation of apoptosis, immune responses, angiogenesis and metastasis. Given that extracellular vesicles (EVs) can serve as potential source for the discovery of clinically useful biomarkers and therapeutic targets, it is of particular interest to study proteomic profiling of HSPs in EVs derived from various biological fluids of cancer patients. Furthermore, a divergent expression of circulating microRNAs (miRNAs) in patient samples has opened new opportunities in exploiting miRNAs as diagnostic tools. Herein, we address the current literature on the expression of extracellular HSPs with particular interest in HSPs in EVs derived from various biological fluids of cancer patients and different types of immune cells as promising targets for identification of clinical biomarkers of cancer. We also discuss the emerging role of miRNAs in HSP regulation for the discovery of blood-based biomarkers of cancer. We outline the importance of understanding relationships between various HSP networks and co-chaperones and propose the model for identification of HSP signatures in cancer. Elucidating the role of HSPs in EVs from the proteomic and miRNAs perspectives may provide new opportunities for the discovery of novel biomarkers of cancer.

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)
          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
          Article 0 comments Cited 3604 times – based on 0 reviews     Review now
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            The biology, function, and biomedical applications of exosomes

            Raghu Kalluri, Valerie LeBleu (2020)
            The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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              Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes.

              Joanna Kowal, Guillaume Arras, Marina Colombo … (2016)
              Extracellular vesicles (EVs) have become the focus of rising interest because of their numerous functions in physiology and pathology. Cells release heterogeneous vesicles of different sizes and intracellular origins, including small EVs formed inside endosomal compartments (i.e., exosomes) and EVs of various sizes budding from the plasma membrane. Specific markers for the analysis and isolation of different EV populations are missing, imposing important limitations to understanding EV functions. Here, EVs from human dendritic cells were first separated by their sedimentation speed, and then either by their behavior upon upward floatation into iodixanol gradients or by immuno-isolation. Extensive quantitative proteomic analysis allowing comparison of the isolated populations showed that several classically used exosome markers, like major histocompatibility complex, flotillin, and heat-shock 70-kDa proteins, are similarly present in all EVs. We identified proteins specifically enriched in small EVs, and define a set of five protein categories displaying different relative abundance in distinct EV populations. We demonstrate the presence of exosomal and nonexosomal subpopulations within small EVs, and propose their differential separation by immuno-isolation using either CD63, CD81, or CD9. Our work thus provides guidelines to define subtypes of EVs for future functional studies.
              Article 0 comments Cited 962 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zarema Albakova
                Journal
                Journal ID (nlm-ta): Transl Oncol
                Journal ID (iso-abbrev): Transl Oncol
                Title: Translational Oncology
                Publisher: Neoplasia Press
                ISSN (Electronic): 1936-5233
                Publication date PMC-release: 15 December 2020
                Publication date Collection: February 2021
                Publication date (Electronic): 15 December 2020
                Volume: 14
                Issue: 2
                Electronic Location Identifier: 100995
                Affiliations
                [a ]Department of Biology, Lomonosov Moscow State University, 199192 Moscow, Russia
                [b ]School of Clinical Medicine, University of Cambridge, CB21TN Cambridge, United Kingdom
                [c ]Department of Pharmacy, BRAC University, 1212 Dhaka, Bangladesh
                [d ]The Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom
                [e ]Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, China
                [f ]Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia
                Author notes
                [* ]Corresponding author. zarema.albakova14@ 123456gmail.com
                Article
                Publisher Item ID: S1936-5233(20)30487-3 Publisher ID: 100995
                DOI: 10.1016/j.tranon.2020.100995
                PMC ID: 7749402
                PubMed ID: 33338880
                SO-VID: 95821d1a-a706-4e9b-adc5-fb07e513a107
                Copyright © © 2020 The Authors. Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 9 October 2020
                Date revision received : 8 November 2020
                Date accepted : 7 December 2020
                Categories
                Subject: Review article

                Keywords: heat shock proteins,extracellular vesicles,extracellular hsps,mirna,biomarker,cancer,hsp, heat shock proteins,mirna, microrna,ms, mass spectrometry,nsclc, non-small cell lung cancer,aml, acute myeloid leukemia,escc, esophageal squamous cell carcinoma,ctc, circulating tumor cells,sccnh, squamous cell carcinoma of the head and neck,gist, gastrointestinal stromal tumor,hcc, hepatocellular carcinoma,dics, ductal carcinoma in situ,cusa, cavitron ultrasonic surgical aspirator,chip, c-terminus of hsp70 interacting protein,hop, hsp70-hsp90 organizing protein,bag, bcl2-associated athanogene,ccrcc, clear cell renal cell carcinoma,hl, hodgkin lymphoma,dlbcl, diffuse large b-cell lymphoma
                Data availability:
                Keywords: heat shock proteins, extracellular vesicles, extracellular hsps, mirna, biomarker, cancer, hsp, heat shock proteins, mirna, microrna, ms, mass spectrometry, nsclc, non-small cell lung cancer, aml, acute myeloid leukemia, escc, esophageal squamous cell carcinoma, ctc, circulating tumor cells, sccnh, squamous cell carcinoma of the head and neck, gist, gastrointestinal stromal tumor, hcc, hepatocellular carcinoma, dics, ductal carcinoma in situ, cusa, cavitron ultrasonic surgical aspirator, chip, c-terminus of hsp70 interacting protein, hop, hsp70-hsp90 organizing protein, bag, bcl2-associated athanogene, ccrcc, clear cell renal cell carcinoma, hl, hodgkin lymphoma, dlbcl, diffuse large b-cell lymphoma

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