Biology, Therapy and Implications of Tumor Exosomes in the Progression of Melanoma

Isola, Allison L.; Eddy, Kevinn; Chen, Suzie

doi:10.3390/cancers8120110

Cited by 43 publications

(52 citation statements)

References 114 publications

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“…In melanoma, EVs, such as exosomes and microvesicles, have been reported to play a predominant role in promoting pre-metastatic niche formation, proliferation, and metastasis [ 16 ]. For example, Dror et al (2016) reported that melanosomal miR-211, which is secreted by melanoma cells and absorbed by fibroblasts, can activate the mitogen-activated protein kinase (MAPK) signaling pathway and induce fibroblast reprogramming into CAFs [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway

Zhou

Yan

Huang

et al. 2018

J Exp Clin Cancer Res

210

179

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BackgroundCancer-associated fibroblasts (CAFs) have been widely reported to promote tumor angiogenesis. However, the underlying mechanisms of the proangiogenic switch of CAFs remain poorly understood. This study aims to clarify the mechanisms underlying the proangiogenic switch of CAFs.MethodsNIH/3T3 cells were treated with B16 and B16F10-derived exosomes. Then the CAFs markers and proangiogenic factors were detected by RT-PCR and Western blot. CCK-8 assay, transwell migration assay, tube formation assay, and in vivo Matrigel plug assay were conducted to determine the proangiogenic capability of CAFs. Western blot and AG490 were used to investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the proangiogenic switch of CAFs. Bioinformatics analysis, luciferase reporter assay, microRNA mimic and inhibitor, and xenograft models were used to investigate the role of mmu-miR-155-5p (miR-155) in the proangiogenic switch of CAFs.ResultsIn this study, we show that melanoma cell-secreted exosomes can induce reprogramming of fibroblasts into CAFs and that exosomal miR-155 can trigger the proangiogenic switch of CAFs. Mechanistically exosomal miR-155 can be delivered into fibroblasts and promote the expression of proangiogenic factors, including vascular endothelial growth factor A (VEGFa), fibroblast growth factor 2 (FGF2), and matrix metalloproteinase 9 (MMP9), by directly targeting suppressor of cytokine signaling 1 (SOCS1). Downregulation of SOCS1 activates JAK2/STAT3 signaling pathway and elevates the expression levels of VEGFa, FGF2, and MMP9 in fibroblasts. Treatment with exosomes containing overexpressed miR-155 can promote angiogenesis, and the reduction of miR-155 in melanoma cell-secreted exosomes alleviates angiogenesis in vitro and in vivo.ConclusionsThese results demonstrate that by promoting the expression of proangiogenic factors in recipient fibroblasts via SOCS1/JAK2/STAT3 signaling pathway, melanoma cell-secreted exosomal miR-155 can induce the proangiogenic switch of CAFs. Although tumor angiogenesis is modulated by various factors, exosomal miR-155 may be a potential target for controlling melanoma angiogenesis and used to set up novel strategies to treat melanoma.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0911-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway

Zhou

Yan

Huang

et al. 2018

J Exp Clin Cancer Res

210

179

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“… Metastasis [ 147 ] miR-135b Multiple myeloma cells endothelial cells FIH-1 Exosomal miR-135b from HR-MM cells enhances endothelial tube formation under hypoxic conditions via the HIF-FIH signaling pathway. Metastasis, angiogenesis [ 148 ] Others Melanoma miR-125b PLX4032-resistant melanoma cell line Primary melanoma cell lines apoptotic pathways miRNA inhibitors increased the fraction of apoptotic cells in LM16-R cells Metastasis [ 149 ] miR-31, − 185, and -34b A375 and SK-MEL-28 Normal melanocytes HAPLN1, GRP78 / Metastasis [ 150 ] miR-222 Metastatic melanoma cell lines Primary melanoma cell lines p27Kip1 Activates the PI3K/AKT pathway. Metastasis [ 151 ] Merkel Cell Carcinoma (MCC) miR-30a, miR-34, miR-142-3p, miR-1539 MCV-positive or -negative tumors / / Upregulation when discriminating between MCPyV-negative and MCPyV-positive MCCs MCPyV infection [ 63 , 152 ] miR-181d Downregulation when discriminating between MCPyV-negative and MCPyV-positive MCCs …”

Section: Introductionmentioning

confidence: 99%

Effect of exosomal miRNA on cancer biology and clinical applications

et al. 2018

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Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.

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“…Particularly, exosomes (Exo) are nano-sized EVs that have been largely investigated in melanoma [4]. Exosomes show the ability to drive a number of specialized functions implicated in the control of proliferation, epithelial-mesenchymal transition (EMT), immune-evasion, and pre-metastatic niche formation [5,6].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression

Mannavola

D’Oronzo

Cives

et al. 2019

IJMS

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Cutaneous melanoma shows a high metastatic potential based on its ability to overcome the immune system’s control. The mechanisms activated for these functions vary extremely and are also represented by the production of a number of extracellular vesicles including exosomes. Other vesicles showing a potential role in the melanoma progression include oncosomes and melanosomes and the majority of them mediate tumor processes including angiogenesis, immune regulation, and modifications of the micro-environment. Moreover, a number of epigenetic modifications have been described in melanoma and abundant production of altered microRNAs (mi-RNAs), non-coding RNAs, histones, and abnormal DNA methylation have been associated with different phases of melanoma progression. In addition, exosomes, miRNAs, and other molecular factors have been used as potential biomarkers reflecting disease evolution while others have been suggested to be potential druggable molecules for therapeutic application.

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Biology, Therapy and Implications of Tumor Exosomes in the Progression of Melanoma

Cited by 43 publications

References 114 publications

Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway

Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway

Effect of exosomal miRNA on cancer biology and clinical applications

Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression

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