The Role of Extracellular Vesicles in Cancer: Cargo, Function, and Therapeutic Implications

Jabalee, James; Towle, Rebecca; Garnis, Cathie

doi:10.3390/cells7080093

Cited by 84 publications

(74 citation statements)

References 175 publications

(290 reference statements)

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“…Although, the reports have demonstrated possible mechanisms by which miRNAs and proteins (other than MMPs) are regulated for their secretion into EVs [ 44 , 45 , 46 ], nevertheless, the mechanisms regarding the secretion of MMPs into EVs remain largely unknown. Recently, it was shown that the stabilization of MMPs in MVBs and their secretion into EVs is regulated by cortactin [ 47 ].…”

Section: Mmps Secretion Into Evsmentioning

confidence: 99%

Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Nawaz

Shah

Zanetti

et al. 2018

Cells

157

138

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Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

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Section: Mmps Secretion Into Evsmentioning

confidence: 99%

Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Nawaz

Shah

Zanetti

et al. 2018

Cells

157

138

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“…Exosomes are released into extracellular space by fusion of multivesicular endosomes with the cell membrane, whereas microvesicles are developed directly from the cell membrane [172]. It has been demonstrated that EVs from neighboring cells can affect various biological properties of cancer cells, such as proliferation, metastasis, hypoxia tolerance, and therapeutic resistance [173,174]. For example, mitochondrial DNA in EVs derived from cancer-associated fibroblasts (CAFs) contributes to the development of resistance to hormone therapy in breast cancer [175].…”

Section: Extracellular Vesicles (Evs)mentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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“…Similarly, in liver cancer cells, CD90-positive cells were found to secrete EVs, that promote tube formation and cell-cell adhesion via the transfer of H19 lncRNA [129]. These results suggest, that subsets of tumor cells secrete EVs carrying a unique set of cargo capable of altering stromal cell phenotypes in specific ways [153].…”

Section: Molecular Cargo Of Tex Influencing Angiogenesis / Tex Convermentioning

confidence: 71%

The role of tumor-derived exosomes in tumor angiogenesis and tumor progression

Głuszko

Mirza

Piszczatowska

et al. 2019

Current Issues in Pharmacy and Medical Sciences

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Exosomes, belonging to the group of extracellular bodies, are released by healthy as well as cancerous cells and serve as a communication pathway. Tumor-derived exosomes (TEX) possess the capacity to reprogram the function of normal cells owing to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment to promote angiogenesis. Blood supply is essential in solid tumor growth and metastasis. The potential of pro-angiogenic changes is enhanced by an increased amount of circulating tumor-derived exosomes in the body fluids of cancer patients. A vascular network is important, since the proliferation, as well as the metastatic spread of cancer cells depends on an adequate supply of oxygen and nutrients, and the removal of waste products. New blood vessels and lymphatic vessels are formed through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. Thousands of patients have received anti-angiogenic therapy to date. Despite their theoretical efficacy, anti-angiogenic treatments have not proved beneficial in terms of long-term survival. Tumor-derived exosomes carrying pro-angiogenic factors might be a target for new anti-cancer therapy.

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The Role of Extracellular Vesicles in Cancer: Cargo, Function, and Therapeutic Implications

Cited by 84 publications

References 175 publications

Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

The role of tumor-derived exosomes in tumor angiogenesis and tumor progression

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