Exosomes in cancer development and clinical applications

Tai, Yu Ling; Chen, Ko-Chien; Hsieh, Jer Tsong; Shen, Tang‐Long

doi:10.1111/cas.13697

Cited by 285 publications

(228 citation statements)

References 71 publications

(169 reference statements)

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“…Recently, exosomes have drawn significant attention as essential mediators of intercellular communication under both physiological and pathological conditions . Recent studies suggested that serum, saliva, or urine exosomal cargos can be used as potential biomarkers for low‐invasive diagnoses of cancers . Diagnosis of chronic liver disease at an early stage instead of irreversible and life‐threatening advanced stages is challenging because of the lack of noninvasive or low‐invasive approaches and long asymptomatic disease progression.…”

Section: Discussionmentioning

confidence: 99%

Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis

et al. 2019

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Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte-derived exosomal long noncoding RNA-H19 (lncRNA-H19) plays a critical role in promoting cholestatic liver injury. However, it remains unclear whether cholangiocyte-derived lncRNA-H19 regulates HSC activation, which is the major focus of this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2 -/-) mouse models were used. Wild-type and H19 maternalΔExon1/+ (H19KO) mice were subjected to BDL. Mdr2 -/-H19 maternalΔExon1/+ (DKO) mice were generated. Exosomes isolated from cultured mouse and human cholangiocytes or mouse serum were used for in vivo transplantation and in vitro studies. Fluorescence-labeled exosomes and flow cytometry were used to monitor exosome uptake by hepatic cells. Collagen gel contraction and bromodeoxyuridine assays were used to determine the effect of exosomal-H19 on HSC activation and proliferation. Mouse and human primary sclerosing cholangitis (PSC)/primary biliary cholangitis (PBC) liver samples were analyzed by real-time PCR, western blot analysis, histology, and immunohistochemistry. The results demonstrated that hepatic H19 level was closely correlated with the severity of liver fibrosis in both mouse models and human patients with PSC and PBC. H19 deficiency significantly protected mice from liver fibrosis in BDL and Mdr2 -/mice. Transplanted cholangiocyte-derived H19-enriched exosomes were rapidly and preferentially taken up by HSCs and HSC-derived fibroblasts, and promoted liver fibrosis in BDL-H19KO mice and DKO mice. H19-enriched exosomes enhanced transdifferentiation of cultured mouse primary HSCs and promoted proliferation and matrix formation in HSC-derived fibroblasts. Conclusion: Cholangiocyte-derived exosomal H19 plays a critical role in the progression of cholestatic liver fibrosis by promoting HSC differentiation and activation and represents a potential diagnostic biomarker and therapeutic target for cholangiopathies. (Hepatology 2019;70:1317-1335).

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Section: Discussionmentioning

confidence: 99%

Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis

et al. 2019

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“…Recent reviews, which devoted to function of exosomes, are focused on cell-to-cell communication, cellular adhesion, migration, invasion, angiogenesis and growth of tumor cells (Azmi et al, 2013;Tai et al, 2018). Therefore, they can no longer be considered simply as garbage bags for throwing out unwanted protein cargo from the cell as originally suggested, necessitating a recalibration of our understanding and of their potential functions in physiological processes.…”

Section: Discussionmentioning

confidence: 99%

Protease Cargo in Circulating Exosomes of Breast Cancer and Ovarian Cancer Patients

Тамкович

Yunusova

Tugutova

et al. 2019

Asian Pac J Cancer Prev

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Breast cancer and ovarian cancer are the most common types of tumor worldwide among women. Despite the active distribution of mammography, the proportion of primary-identified breast cancer patients (BCPs) at an advanced stage of the disease remains high (Witten and Parker, 2018). Most ovarian cancer patients (OCPs) are diagnosed at an advanced stage also and 70% of patients present with lymph node metastasis and ascites fluids (Dong et al., 2014). Cancer patients with metastasis have a higher rate of treatment failure and mortality (Ferlay et al., AbstractBackground: As is known, exosomes play an important role in promoting progression of cancers by increasing its invasive potential. The aim of this study was to evaluate the levels of tetraspanine-associated (ADAM-10) and tetraspanine-nonassociated proteases (20S proteasomes) in exosomes from culture medium, plasma exosomes of patients with breast tumors and plasma and ascites of ovarian tumor patients. Methods: MCF-7 and SVO-3 culture mediums and blood samples from healthy females (n = 30, HFs), patients with diffuse dyshormonal dysplasia of the breast (n=28, BBTPs), breast cancer patients (n=32, BCPs), borderline ovarian tumor patients (n=20, BOTPs) and blood and ascites samples ovarian cancer patients (n=35, OCPs) were included in the study. Exosomes from plasma, ascites and culture mediums were isolated and characterized in according to Extracellular Vesicles Society. The expression levels of 20S proteasome and ADAM-10 in exosomes were determined using flow cytometry and western blot analysis, correspondingly. Results: The subpopulation composition of the exosomes from MCF-7 culture medium and from blood plasma of HFs and breast diseases patients is similar, however CD9/CD24 subpopulation significantly increased at cell supernatant. The similar results was obtained for exosomes from SVO-3 medium and blood plasma and ascites of ovary tumor patients, but CD9/CD24 subpopulation significantly decreased at cells and illness samples, however CD63/CD24 exosomes increased significantly from cell supernatant. 20S proteasome level is significantly increased in exosomes from MCF-7 and SVO-3 culture medium, breast tumor patients and OCPs plasma in comparison to HUVEC culture medium and HFs plasma samples. At CD9-positive exosomes from BCPs plasma and MCF-7 was reveal a high expression of ADAM-10 and low expression is from BBDPs plasma and ovarian tumor patients plasma/ ascites samples. Exosomes from ascites OCP had high expression of ADAM-10 in the CD24-positive subpopulation. Conclusion: Breast and ovarian cancer development is connected with functioning of immune proteasome forms in plasma and ascites exosomes, while increased ADAM10 expression at CD9-positive exosome was associated with breast cancer and at CD24-positive subpopulation -with ovarian cancer. Obtained data confirm role of exosomal proteases in tumor progression.

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“…Adapted with permission from [156]. Copyright (2017) American Chemical Society inhibition of the exosome production, secretion, cell-tocell communication as well as removal of exosomalspecific loads [179,180]. Also given their stability in systemic circulation and tumor-based specificity, exosomes are studied for their abilities to deliver anti-cancer agents [181].…”

Section: Exosomesmentioning

confidence: 99%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

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Exosomes in cancer development and clinical applications

Cited by 285 publications

References 71 publications

Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis

Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis

Protease Cargo in Circulating Exosomes of Breast Cancer and Ovarian Cancer Patients

Tumor microenvironment complexity and therapeutic implications at a glance

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