Cancer-testis antigens MAGEA proteins are incorporated into extracellular vesicles released by cells

Kuldkepp, Anneli; Karakai, Magda; Toomsoo, Eve; Reinsalu, Olavi; Kurg, Reet

doi:10.18632/oncotarget.26979

Cited by 8 publications

(15 citation statements)

References 41 publications

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“…MAGEA is normally expressed in the testis or placenta and plays a crucial role in germ cell development [121]. Aberrantly high MAGEA expression is usually found in invasive malignant tumors, indicating poor prognosis [122].…”

Section: Mir-448mentioning

confidence: 99%

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Jiao

Qian

et al. 2019

Cells

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Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.

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Section: Mir-448mentioning

confidence: 99%

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Jiao

Qian

et al. 2019

Cells

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“…MAGEA4-EVs used in this study were isolated and purified from cell culture media as described previously [ 54 ]. Briefly, for the production of MAGEA4-EVs, mouse COP5-EBNA fibroblast cells were transfected with a MAGEA4-expressing plasmid, and the isolation and purification of EVs were performed 72 h post-transfection using differential ultracentrifugation.…”

Section: Resultsmentioning

confidence: 99%

“…Corso et al [ 89 ] showed that a variety of EV markers with different localization are able to label EVs with different efficiencies, whereas transmembrane tetraspanins performed the best and soluble proteins the worst. Considering that MAGEA4 is a membrane-associated protein [ 53 , 54 ], it is able to display the recombinant protein on the surface of EVs noticeably well. This characteristic has the potential to be adapted for further EV-based application including labeling EVs for in vivo biological studies or loading EVs with recombinant proteins or peptides.…”

Section: Discussionmentioning

confidence: 99%

“…All these efforts describe MAGEA4 as a highly valued candidate for developing cancer-targeting immunotherapies. Previously, we have reported that MAGEA4 is metabolically incorporated into EVs and retrovirus Gag protein-induced virus-like particles (VLP) in cancer cells as well as in cells ectopically expressing the protein where the MAGEA4 protein is exposed on the surface of the vesicles [ 53 , 54 ]. This phenomenon is highly intriguing, considering that MAGEA4 is a soluble cytoplasmic protein in cells.…”

Section: Introductionmentioning

confidence: 99%

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MAGEA4 Coated Extracellular Vesicles Are Stable and Can Be Assembled In Vitro

Reinsalu

Samel

Niemeister

et al. 2021

IJMS

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Extracellular vesicles (EVs) are valued candidates for the development of new tools for medical applications. Vesicles carrying melanoma-associated antigen A (MAGEA) proteins, a subfamily of cancer-testis antigens, are particularly promising tools in the fight against cancer. Here, we have studied the biophysical and chemical properties of MAGEA4-EVs and show that they are stable under common storage conditions such as keeping at +4 °C and −80 °C for at least 3 weeks after purification. The MAGEA4-EVs can be freeze-thawed two times without losing MAGEA4 in detectable quantities. The attachment of MAGEA4 to the surface of EVs cannot be disrupted by high salt concentrations or chelators, but the vesicles are sensitive to high pH. The MAGEA4 protein can bind to the surface of EVs in vitro, using robust passive incubation. In addition, EVs can be loaded with recombinant proteins fused to the MAGEA4 open reading frame within the cells and also in vitro. The high stability of MAGEA4-EVs ensures their potential for the development of EV-based anti-cancer applications.

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“…Patients received three weekly vaccines up to six vaccinations. The dendritic cell immunotherapy was safe with no apparent toxicity, however dendritic cell vaccine therapy was associated with a significant antitumour response in only two out of the 12 vaccinated patients with no evidence of clinical benefit Krishnadas et al (2015). used dendritic cells pulsed with overlapping peptides derived from full-length MAGE-A1, MAGE-A3 and NY-ESO-1 antigen tumours to treat relapsed/refractory solid tumours, including Ewing's sarcoma and osteosarcoma (10 patients aged between 2.5 to 15 years with relapsed disease).…”

mentioning

confidence: 93%

Bone sarcomas in the immunotherapy era

Heymann

Schiavone

Heymann

2020

British J Pharmacology

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Bone sarcomas are primary bone tumors which occur mainly in children and adolescents, in the form of osteosarcoma and Ewing sarcoma, and in people in their 40s, in the form of chondrosarcoma. The last four decades have been characterized by the development of therapeutic approaches based on drug combinations, but with no real improvement in overall survival. Recent progress made in the field of oncoimmunology has made it possible to better understand the crucial role played by immune infiltrate in the oncologic process and has led to recent clinical trials with a common aim: reprogramming the immune system in order to facilitate cancer cell recognition. Similarly, immune infiltrates of bone sarcomas have been characterized and the first molecular profiling identified potential immune therapeutic targets, which have been used for designing ongoing clinical trials. Unfortunately, the objective clinical responses in clinical trials remain anecdotal but highlight the necessity to better characterize tumor microenvironment of bone sarcoma to unlock the immunotherapeutic response especially in their pediatric forms. Bone sarcomas have thus entered the immunotherapy era. The present review gives a brief overview of the most recent developments in immunotherapies in bone sarcomas.

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Cancer-testis antigens MAGEA proteins are incorporated into extracellular vesicles released by cells

Cited by 8 publications

References 41 publications

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

MAGEA4 Coated Extracellular Vesicles Are Stable and Can Be Assembled In Vitro

Bone sarcomas in the immunotherapy era

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