MiRNA in melanoma-derived exosomes

Gajos-Michniewicz, Anna; Duechler, Markus; Czyż, Małgorzata

doi:10.1016/j.canlet.2014.02.004

Cited by 97 publications

(72 citation statements)

References 128 publications

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“…There is increasing evidence that the effect of exosomes on target cells is mainly dependent on their intravesicular miRNA expression (36)(37)(38). Here, we found that fluorescently labeled exosomes were internalized into endothelial cells (see Figure E3), where they could be implicated in a myriad of important processes (39)(40)(41)(42)(43)(44). Based on the selectivity of miRNA loading into extracellular vesicles (EV) and their stability (45), potential differences in miRNA exosomal cargo were identified, and were compatible with previous work implicating exosomal miRNAs not only in angiogenesis and other vascular phenomena (46,47), while also suggesting the possibility that exosomes may provide therapeutic opportunities (48).…”

Section: Discussionmentioning

confidence: 53%

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Khalyfa¹,

Kheirandish‐Gozal²,

Khalyfa³

et al. 2016

Am J Respir Crit Care Med

103

110

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Rationale: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells.Objectives: To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status.Methods: Obese children (body mass index z score .1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cellsubstrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays.Measurements and Main Results: Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways.Conclusions: These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.

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Section: Discussionmentioning

confidence: 53%

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Khalyfa¹,

Kheirandish‐Gozal²,

Khalyfa³

et al. 2016

Am J Respir Crit Care Med

103

110

View full text Add to dashboard Cite

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“…Several miRs as exosome cargos have been implicated as mediators of angiogenesis and metastasis. Melanoma-derived exosomes containing miR-9 have been shown to activate JAK-STAT signaling in ECs (116). Exosomal cancer cell-derived miR-210 has been identified as another angiogenesis and metastastis-promoting miRNA (117), which is upregulated in exosomes derived under hypoxic conditions (118), and its transfer to ECs was shown to be dependent on exosome-formation promoting neutral sphingomyelinase 2 (nSMase 2) (119).…”

Section: Metastasis-related Interactions Between Cancer Cell-derived mentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

167

133

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Abstract. Exosomes are important contributors to cellMetastases are responsible for the death of a large majority of cancer patients despite considerable progress in surgical techniques, radiotherapy, chemotherapy and targeted therapies including immuno-therapy (1). A dramatic reduction of metastatic burden has been observed, however, tumor elimination is almost always incomplete. This phenomenon is based on drug resistance, which is due to adaptation of intracellular pathways or on activation of survival-supporting autocrine and paracrine pathways and several secreted factors expressed by drug-sensitive tumor cells after therapy (2). Metastasis can occur through release of cancer cells from the primary tumor into body cavities that holds true for ovarian and CNS tumors, or via hematogeneous and lymphatic vessels of the circulatory system (3). Metastases of some tumors are directed besides to lymph nodes to mainly one type of organ only, such as prostate cancer to the bones, pancreatic cancer and uveal melanoma to the liver, whereas tumors such as melanoma, breast-and lung cancer can colonize several types of organs (3). Tumor cells have been found in the blood of patients with early-stage cancer and in some cases even before the primary tumor has been diagnosed (4, 5). Recently, making use of single-cell expression profiling, it has been shown that early metastatic cells possess a stem-like gene signature and give rise to heterogeneous metastases (6). The metastatic process is characterized by a defined sequence of events (7,8). Initial steps are detachment from the extracellular matrix (ECM), invasion into the surrounding tissue and proteolysis of the basement membrane. After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10). After extravasation, colonization and outgrowth in the parenchyma of distant organs are the following steps. A common theme of the metastatic process is settlement of disseminated tumor cells (DTCs) into latency (dormancy), which can last from several months to decades (11). It has been observed that DTCs are recruited into pre-metastatic niches that support their survival by interactions with endothelial, myeloid cells, fibroblasts and other types of cells. After adaptation to the host microenvironment and suppression of an anti-tumoral immune response, DTCs are activated by not yet completely resolved mechanisms. Finally their outgrowth is based on an angiogenic switch mediated by pro-angiogenic factors and establishment of a vascular network to support the metabolic demands of colonizing tumor cells (12). In the follo...

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“…Melanoma is the most malignant tumor of the skin tumors (71). Due to the aggressiveness, ease of distant metastasis and treatment resistance, melanoma has a high mortality rate (72)(73)(74). Early diagnosis and treatment is therefore particularly important.…”

Section: Exosomes and Skin Cancermentioning

confidence: 99%

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

Liu

Wang

2018

biom rep

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Abstract. Exosomes are one of the most potent intercellular communicators, which are able to communicate with adjacent or distant cells. Exosomes deliver various bioactive molecules, including membrane receptors, proteins, mRNA and microRNA, to target cells and serve roles. Recent studies have demonstrated that exosomes may regulate the functions and diseases of the skin, which is the largest organ of the human body. The abnormal functions of the skin lead to the progression of scleroderma, melanoma, baldness and other diseases. A previous study has demonstrated that epithelial progenitor cells are rich in several subunits of exosomes that may maintain the proliferative capacity of these epithelial progenitor cells, which is essential for the development of the epidermis. Exosomes derived from human adipose mesenchymal stem cells accelerate skin wound healing by optimizing fibroblast properties; this is beneficial for the recovery of postoperative and other wounds. Exosomes derived from adipocytes promote melanoma migration and invasion through fatty acid oxidation; therefore, in the clinic, it may be possible to improve the prognosis of patients with melanoma by reducing their body fat content. Exosomes derived from keratinocytes modulate melanocyte pigmentation, which has been utilized as a novel mechanism for the regulation of pigmentation in conditions including Moynahan syndrome and albinism. Meanwhile, scleroderma patients with vascular abnormalities may experience decreased serum exosome levels; it may therefore be possible to detect the exosome content in sera in order to diagnose and treat scleroderma. In addition, the use of exosomes has been suggested to promote or enhance hair growth, which has been demonstrated to be highly effective. These studies have provided new opportunities and therapeutic strategies for understanding how exosomes regulate intercellular communication in pathological processes of the skin.

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MiRNA in melanoma-derived exosomes

Cited by 97 publications

References 128 publications

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

The Multiple Roles of Exosomes in Metastasis

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

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