The critical role of exosomes in tumor biology

Jiang, Ke‐Jian; Dong, Chengyong; Yin, Zhenzhen; Li, Rui; Wang, Qi; Wang, Liming

doi:10.1002/jcb.27813

Cited by 9 publications

(7 citation statements)

References 142 publications

(243 reference statements)

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“…The organotropism described for tumor-derived exosomes to the tumor site and premetastatic niche could hold the key for designing highly efficient anticancer therapies targeting metastatic cancer with minimum side effects [9, 26]. However, the main drawback for the application of this approach is the lack of more in-depth understanding of their molecular composition and function, raising safety concerns that must be resolved prior to promote their therapeutic application [10]. Moreover, the low yield, highly laborious, costly, and time-consuming methods of production for cell-derived exosomes, together with a lack of standardization for relevant processes such are determining their physicochemical properties and drug loading capacity, are additional challenges to overcome [27–29].…”

Section: Discussionmentioning

confidence: 99%

“…Using tumor-derived exosomes will provide additional competitive advantages for the selective delivery of anticancer therapies not only to the primary tumor but also to metastasis and even to the premetastatic niche, owing to their intrinsic organotropic tumor-homing properties [8, 9]. Besides, tumor-derived exosomes are also involved in a wide range of biological processes, including tumor progression, metastasis formation, and drug resistance, mechanisms that still remain poorly understood, making it necessary to generate a deeper knowledge before considering their safe application in therapeutics [10, 11].…”

Section: Introductionmentioning

confidence: 99%

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Exosome-mimetic nanoplatforms for targeted cancer drug delivery

et al. 2019

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Background Lack of effective tumor-specific delivery systems remains an unmet clinical challenge for successful translation of innovative therapies, such as, therapeutic oligonucleotides. In the past decade, exosomes have been suggested to be ideal drug delivery systems with application in a broad range of pathologies including cancer, due to their organotropic properties. Tumor-derived exosomes, having tumor-homing properties, can efficiently reach cancer cells and therefore behave as carriers for improved drug delivery to the primary tumor and metastases. However, due to their complex composition, and still undefined biological functions, safety concerns arise hampering their translation to the clinics. Results We propose here the development of exosome-mimetic nanosystems (EMNs) that simulate natural tumor-derived exosomes with respect to their structure and functionality, but with a controlled composition, for the targeted delivery of therapeutic oligonucleotides to lung adenocarcinoma cells (microRNA-145 mimics). Making use of the well-known liposome technology, EMNs can be engineered, loaded with the therapeutic compounds, and tailored with specific proteins (integrin α6β4) providing them organotropic properties. EMNs show great similarities to natural exosomes with respect to their physicochemical properties, drug loading capacity, and ability to interact with the cancer target cells in vitro and in vivo, but are easier to manufacture, can be produced at high yields, and are safer by definition. Conclusions We have designed a multifunctional nanoplatform mimicking exosomes, EMNs, and proved their potential to reach cancer cells with a similar efficient that tumor-derived exosomes but providing important advantages in terms of production methodology and regulations. Additionally, EMNs are highly versatile systems that can be tunable for a broader range of applications. Electronic supplementary material The online version of this article (10.1186/s12951-019-0517-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exosome-mimetic nanoplatforms for targeted cancer drug delivery

et al. 2019

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“…Approximately, 50% of CRC patients are deceased as a consequence of late detection of advanced disease with localized or distant metastases (3). These phenomena highlight and underscore a need for the identification and development of robust and inexpensive screening biomarkers that are non-invasive and facilitate the early detection of CRC such as fluid biopsy based on blood contents including cell-free DNA (4), circulating tumor cells (5), and exosomes (6).…”

Section: Introductionmentioning

confidence: 99%

Circulating Exosomal miR-150-5p and miR-99b-5p as Diagnostic Biomarkers for Colorectal Cancer

et al. 2019

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Background: Circulating exosomal miRNAs are potential non-invasive biomarkers for colorectal cancer. The present study aimed to validate the novel sensitive and specific exosomal miRNA biomarkers for diagnosing colorectal cancer (CRC).Patients and Methods: Exosomes isolated from the serum of CRC patients and healthy donors by ultracentrifugation were characterized using TEM, qNano, and immunoblotting. The exosomes from 2 healthy donors and 4 CRC patients were subjected to RNA isolation and miRNA sequencing. The differently expressed miRNAs from 165 primary CRC patients and 153 healthy donors were substantiated by RT-qPCR.Results: The RNA-sequence data analysis revealed that 29 exosomal miRNAs (20 downregulated and 9 upregulated) with >1.5-fold difference between CRC patients and healthy donors were selected. The serum exosomal miR-99b-5p and miR-150-5p levels were significantly downregulated in CRC patients as compared to healthy donors (p < 0.0001 and p < 0.0001, respectively) and benign disease (p = 0.009 and p < 0.0001, respectively). The expression levels of exosomal miR-99b-5p and miR-150-5p were significantly decreased in early CRC patients as compared to healthy donors (p < 0.0001 and p < 0.0001, respectively). The expression levels of exosomal miR-99b-5p and miR-150-5p were significantly increased postoperatively (p = 0.0058 and p < 0.0001, respectively).Conclusions: The present study demonstrated that serum exosomal miRNAs are promising, sensitive, specific, and non-invasive diagnostic biomarkers for CRC.Impact: This is the first study to specifically identify exosomal miR-99b-5p and miR-150-5p associated with CRC. This study, therefore, might deepen the understanding of tumor-derived exosomes for CRC diagnosis.

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“…Exosomes from heat-treated gastric cancer malignant ascites have improved immunogenicity, being able to promote dendritic cell maturation and induce a tumor-specific cytotoxic T cell response ( 66 ). The organotropic factors, such as integrins on the exosome surface, could be used to improve targeting specificity and deliver drugs to specific tissues ( 129 ). However, it remains unknown whether exosome-based drug delivery could be used to prevent or treat gastric cancer metastasis to a specific organ.…”

Section: Implications and Perspectivesmentioning

confidence: 99%

Exosomes Promote Pre-Metastatic Niche Formation in Gastric Cancer

Gao

Song

et al. 2021

Front. Oncol.

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Gastric cancer has a high rate of metastasis, during which pre-metastatic niches (PMN) provide a supportive environment for the upcoming tumor cells. Exosomes are bilayer vesicles secreted by cells containing biological information that mediates communication between cells. Using exosomes, gastric cancer cells establish PMN remotely in multifarious perspectives, including immunosuppression, stroma remodeling, angiogenesis, mesothelial mesenchymal transformation, and organotropism. In turn, the cell components in PMN secrete exosomes that interact with each other and provide onco-promoting signals. In this review, we highlight the role of exosomes in PMN formation in gastric cancer and discuss their potential values in gastric cancer metastasis diagnosis, prevention, and treatment.

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The critical role of exosomes in tumor biology

Cited by 9 publications

References 142 publications

Exosome-mimetic nanoplatforms for targeted cancer drug delivery

Exosome-mimetic nanoplatforms for targeted cancer drug delivery

Circulating Exosomal miR-150-5p and miR-99b-5p as Diagnostic Biomarkers for Colorectal Cancer

Exosomes Promote Pre-Metastatic Niche Formation in Gastric Cancer

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