Exploring the potential of engineered exosomes as delivery systems for tumor-suppressor microRNA replacement therapy in ovarian cancer

Kobayashi, Masaki; Sawada, Kenjiro; Miyamoto, Mitsuhiro; Shimizu, Ayaka; Yamamoto, Misa; Kinose, Yasuto; Nakamura, Koji; Kawano, Mahiru; Kodama, Michiko; Hashimoto, Kae; Kimura, Tadashi

doi:10.1016/j.bbrc.2020.04.076

Cited by 89 publications

(77 citation statements)

References 25 publications

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“…Exosomes also carry signal transduction proteins, for example, receptor tyrosine kinases and membrane transport and fusion proteins, such as the GTPases Rab5 and Rab7 (11). Studies have also reported that nucleic acids are carried by exosomes, comprising of a diverse mix of DNA (13,14), RNA (15), lncRNA (16) and miRNA (17,18) molecules. Exosomal miRs (miR-15, -16, 151 and -375) can promote angiogenesis and tumor progression in the TME (11).…”

Section: Biological Characteristics Of Exosomesmentioning

confidence: 99%

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

et al. 2021

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Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.

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Section: Biological Characteristics Of Exosomesmentioning

confidence: 99%

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

et al. 2021

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“…The therapeutic effects of exosomes, and EVs in general, have already been extensively demonstrated, both when considering their natural properties and cargo and when engineered with drug molecules [144]. In particular, clinical trials focusing on exosome-based treatments have been reported in different clinical fields, such as cardiology [145][146][147], neurology [148][149][150], oncology [151][152][153], and immunology [154]. Along with all the other aspects mentioned in this review, the use of exosomes as therapeutic tools in oncohematology has only been recently explored and reported.…”

Section: Small Evs As Potential Therapeutic Toolsmentioning

confidence: 99%

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

Bernardi

Farina

2021

Biology

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Extracellular vesicles (exosomes, in particular) are essential in multicellular organisms because they mediate cell-to-cell communication via the transfer of secreted molecules. They are able to shuttle different cargo, from nucleic acids to proteins. The role of exosomes has been widely investigated in solid tumors, which gave us surprising results about their potential involvement in pathogenesis and created an opening for liquid biopsies. Less is known about exosomes in oncohematology, particularly concerning the malignancies deriving from myeloid lineage. In this review, we aim to present an overview of immunomodulation and the microenvironment alteration mediated by exosomes released by malicious myeloid cells. Afterwards, we review the studies reporting the use of exosomes as disease biomarkers and their influence in response to treatment, together with the recent experiences that have focused on the use of exosomes as therapeutic tools. The further development of new technologies and the increased knowledge of biological (exosomes) and clinical (myeloid neoplasia) aspects are expected to change the future approaches to these malignancies.

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“…Furthermore, exosomes are a delivery systems with low immunogenicity and toxicity that are not recognized by the mononuclear phagocyte system (82). These special properties of exosomes make them appropriate to serve as targeted delivery systems in cancer therapy (83,84). Recently, Nie et al (85) demonstrated that miR-126 loaded into 231-Exo (miRNA-231-Exo) led to an effective inhibitory effect on proliferation and migration in A549 lung cancer cells via the interruption of the PTEN/PI3K/AKT signaling pathway.…”

Section: Mir-126 As a Potential Target For Lung Cancer Therapymentioning

confidence: 99%

MicroRNA‑126: A new and promising player in lung cancer (Review)

Chen

Zhao

et al. 2020

Oncol Lett

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Lung cancer is one of the most common malignant tumors associated with cancer death; however, the mechanisms involved in lung tumor development have not been completely elucidated, which impedes the advancement of clinical diagnosis and therapy. MicroRNA-126 (miR-126) is an important member of the microRNA family and is encoded by intron 7 of epidermal growth factor-like domain-containing gene 7. Increasing evidence has demonstrated that miR-126, as a distinct endothelial-enriched miRNA and new tumor suppressor gene, serves a promising role in the occurrence, development and metastasis of various types of cancer, including liver cancer, colorectal cancer, melanoma and lung cancer. In the present review, the current knowledge of the role of miR-126 in lung cancer growth, metastasis, diagnosis and prognosis as well as therapy was summarized, which may provide new insights on the biological roles of miRNAsin lung cancer and facilitate the ultimate development of miRNA-based therapies in clinical patients with non-small cell lung cancer.

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Exploring the potential of engineered exosomes as delivery systems for tumor-suppressor microRNA replacement therapy in ovarian cancer

Cited by 89 publications

References 25 publications

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

MicroRNA‑126: A new and promising player in lung cancer (Review)

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