INDUCTION OF TUMOR-ASSOCIATED PHENOTYPE IN NORMAL FIBROBLASTS BY GLIOMA CELL APOPTOTIC BODIES

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Abstract

The key cellular component of solid tumors, including gliomas, are tumor-associated fibroblasts (TAFs), which support the growth of malignant cells, stimulate their invasion and metastasis, induce chemoresistance and suppress the antitumor immune response. TAFs are formed from resident stromal cells under the influence of the tumor cell secretome, including growth factors, chemokines, and extracellular vesicles. Communication between malignant cells and TAFs occurs through direct cell-cell contacts and by mutual exchange of secreted molecules and membrane vesicles. In this work, apoptotic bodies (apoBD) were obtained from two types of glioma cells (T98g cell line and cells isolated from glioblastoma patient biopsy) and characterized by surface markers. The surface of tumor apoBD contains glioblastoma tumor-associated markers such as ganglioside GD2 and antigen A2B5. It was demonstrated that glioma apoBDs have decreased levels of "don't eat me" molecules and increased level of "eat me" signal compared to the original intact glioma cells. On the one hand, glioma apoBDs reduced the viability of normal dermal fibroblasts in a dose-dependent manner, but on the other hand, induced their transformation into the inflammatory subtype of TAFs. The iTAFs obtained in this way demonstrated enhanced transcription of genes encoding cytokines, chemokines and growth factors, including IL17A, IL18, IL33, IFN-γ, CCL3, CCL5, CXCL1, CXCL5, CXCL10, CXCL12, TGFB1, and TNF, responsible for maintaining both tumorigenesis itself and the ability of fibroblasts to maintain it. It was found that glioma apoBDs are able to transfer tumor-associated markers, ganglioside GD2 and antigen A2B5, into normal fibroblasts, and the effects of anti-GD2 ADC on TAFs were investigated. This result may become a prerequisite for the development of targeted drugs that are effective not only against tumor cells but also against tumor stroma.

About the authors

K. V Kovalskaya

Institute of Biomedical Chemistry

Moscow, Russia

M. M Titov

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Moscow, Russia

K. K Baskaev

Institute of Biomedical Chemistry

Moscow, Russia

A. Y Lupatov

Institute of Biomedical Chemistry

Moscow, Russia

D. M Potashnikova

Lomonosov Moscow State University, Faculty of Biology

Moscow, Russia

O. Y Susova

N. N. Blokhin National Medical Research Center of Oncology

Moscow, Russia

Y. S Kim

Institute of Biomedical Chemistry

Moscow, Russia

K. N Yarygin

Institute of Biomedical Chemistry; Russian Medical Academy of Postgraduate Education of the Ministry of Healthcare of the Russian Federation

Moscow, Russia; Moscow, Russia

R. V Kholodenko

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS

Moscow, Russia

I. V Kholodenko

Institute of Biomedical Chemistry

Email: irkhol@yandex.ru
Moscow, Russia

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

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2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».