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      Formation, contents, functions of exosomes and their potential in lung cancer diagnostics and therapeutics

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          Abstract

          Lung cancer is the leading cause of cancer‐related death worldwide due to diagnosis in the advanced stage and drug resistance in the subsequent treatments. Development of novel diagnostic and therapeutic methods is urged to improve the disease outcome. Exosomes are nano‐sized vehicles which transport different types of biomolecules intercellularly, including DNA, RNA and proteins, and are implicated in cross‐talk between cells and their surrounding microenvironment. Tumor‐derived exosomes (TEXs) have been revealed to strongly influence the tumor microenvironment, antitumor immunoregulatory activities, tumor progression and metastasis. Potential of TEXs as biomarkers for lung cancer diagnosis, prognosis and treatment prediction is supported by numerous studies. Moreover, exosomes have been proposed to be promising drug carriers. Here, we review the mechanisms of exosomal formation and uptake, the functions of exosomes in carcinogenesis, and potential clinical utility of exosomes as biomarkers, tumor vaccine and drug delivery vehicles in the diagnosis and therapeutics of lung cancer.

          Abstract

          Formation and secretion of exosomes by donor cells and uptake of exosomal contents by recipient cells. Diverse applications of tumor‐derived exosomes in lung cancer management.

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          Most cited references167

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Tumour exosome integrins determine organotropic metastasis

            Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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              The biology and function of fibroblasts in cancer.

              Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.
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                Author and article information

                Contributors
                yuanyc@csu.edu.cn
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                04 November 2021
                December 2021
                : 12
                : 23 ( doiID: 10.1111/tca.v12.23 )
                : 3088-3100
                Affiliations
                [ 1 ] Department of Thoracic Surgery, The Second Xiangya Hospital Central South University Changsha China
                Author notes
                [*] [* ] Correspondence

                Yunchang Yuan, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

                Email: yuanyc@ 123456csu.edu.cn

                Author information
                https://orcid.org/0000-0001-8923-0504
                https://orcid.org/0000-0003-4740-2923
                Article
                TCA14217
                10.1111/1759-7714.14217
                8636224
                34734680
                49dd7e6c-458f-4fa4-ae63-539f4d788d6a
                © 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 18 October 2021
                : 03 September 2021
                : 19 October 2021
                Page count
                Figures: 3, Tables: 0, Pages: 13, Words: 12902
                Funding
                Funded by: Key Research and Development Program of Hunan Province of China , doi 10.13039/501100019091;
                Award ID: 2018SK21215
                Categories
                Review
                Review
                Custom metadata
                2.0
                December 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.9 mode:remove_FC converted:01.12.2021

                biomarker,diagnosis,exosome,lung cancer,tumor‐derived exosome

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