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IL-6 orchestrates the migration of urokinase receptor-deficient neuroblastoma cellsстатья
Статья опубликована в журнале из списка RSCI Web of Science
Статья опубликована в журнале из перечня ВАКСтатья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 21 мая 2019 г.
- Авторы: Semina E.V., Rysenkova K.D., Rubina K.A., Tkachuk V.A.
- Журнал: Онтогенез
- Том: 49
- Номер: 4S
- Год издания: 2018
- Первая страница: 40
- Последняя страница: 41
- DOI: 10.1134/S0475145018010081
- Аннотация: Relevance Neuroblastoma is a extracranial tumor of the nervous system with a highly invasive phenotype. Previously it was shown that activation of urokinase and its receptor (uPAR) has a stimulating effect on migration and invasion of most cancer cells. Here we show a new mechanism of neuroblastoma migration involving IL-6 upregulation. Purpose of the research To determine the role of the uPAR in the migration of neuroblastoma cells. Research methods Downregulation of uPAR (Neuro2a-ΔuPAR) in Neuro2a murine neuroblastoma cell line was carried out using CRISPR/Cas9. Overexpression of uPAR (Neuro2a-uPAR) was performed using plasmid transfection with cDNA of murine uPAR. uPAR and IL-6 content was evaluated by Western blot. Wound scratch assay was performed to evaluate the migration capacity of cells. Results were analyzed within 24 h using Leica AF6000LX detection system and data counting by Wound Healing Tool (ImageJ software). Results We investigated the effect of uPAR downregulation on migration of Neuro2a cells in the presence of its genuine ligand uPA. We demonstrated that the uPA-mediated Neuro2a migration inversely depend on uPAR expression: administration of uPA within 12 h of the experiment resulted in a 1.5-fold increase in Neuro2a-ΔuPAR migration to the scratch wound compared to control and Neuro2a-uPAR cells. After 24 h Neuro2a-ΔuPAR cells almost completely (up to 79%, p<0.05) recolonized the scratch wound, while control and Neuro2a-uPAR cells recolonized it to a significantly less extent (9 and 12%, correspondingly). Furthermore in Neuro2a-ΔuPAR cell we detected a significant upregulation of IL-6 expression - a highly potent migratory and metastatic cytokine for neuroblastomas. Conclusions These results allow us to propose a novel mechanism of uPAR-dependent neuroblastoma cell migration involving IL-6. Source of funding: Grant №14-24-00086 of the Russian Science Foundation and Grant №14-50-00029 of the Russian Foundation of Basic Research. Keywords: uPAR, IL-6, neuroblastoma, cell migration, CRISPR/Cas9
- Добавил в систему: Семина Екатерина Владимировна
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Полный текст | Специальный выпуск журнала «Онтогенез», том 49, 4 Приложение | Ontogenez_2018_t._49_pp.1-4_40-41.pdf | 3,9 МБ | 5 декабря 2018 [RysenkovaKD] |
| 2. | Полный текст | Сборник тезисов | CTERP-2018-Abstracts.pdf | 907,5 КБ | 15 мая 2018 [RysenkovaKD] |