دورية أكاديمية
Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment.
| العنوان: | Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment. |
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| المؤلفون: | Alonso-Crisostomo, Luz, Trendell, Jennifer, Ferraresso, Marta, Bailey, Shivani, Ward, Dawn, Scurlock, Zachary GL, Wenlock, Stephanie C, Bastos, Carlos AP, Jugdaohsingh, Ravin, Faria, Nuno J, Enright, Anton J, Scarpini, Cinzia G, Coleman, Nicholas, Murray, Matthew J |
| بيانات النشر: | Wiley //dx.doi.org/10.1002/ijc.34697 Int J Cancer |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | extracellular vesicles, germ cell tumour, microRNA, testicular, tumour microenvironment, Male, Female, Humans, MicroRNAs, Seminoma, Endothelial Cells, Tumor Microenvironment, Biomarkers, Tumor, Testicular Neoplasms, Neoplasms, Germ Cell and Embryonal |
| الوصف: | Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; text/xml |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/355895Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/355895Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.8BBCD855 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |