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Biomolecules
Volume 14
Issue 4
10.3390/biom14040466
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Article

Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile

by
Irina Arutyunyan
1,2,3,
Anna Soboleva
2,3,
Dorzhu Balchir
2,
Enar Jumaniyazova
2,*,
Vera Kudelkina
3,
Andrey Elchaninov
1,2,3 and
Timur Fatkhudinov
1,2,3
1
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov Ministry of Healthcare of the Russian Federation, 4 Oparina Street, 117997 Moscow, Russia
2
Research Institute of Molecular and Cellular Medicine, RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia
3
Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution Petrovsky National Research Centre of Surgery, 3 Tsyurupy Street, 117418 Moscow, Russia
*
Author to whom correspondence should be addressed.
Biomolecules 2024, 14(4), 466; https://doi.org/10.3390/biom14040466
Submission received: 24 December 2023 / Revised: 6 April 2024 / Accepted: 9 April 2024 / Published: 10 April 2024
(This article belongs to the Special Issue Organoids and Advanced 3D Models in Biomedical Research)
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Abstract

Hyaluronic acid (HA), a major glycosaminoglycan of the brain extracellular matrix, modulates cell behaviors through binding its receptor, Cd44. In this study, we assessed the influence of HA on high-grade brain tumors in vitro. The model comprised cell cultures derived from six rodent carcinogen-induced brain tumors, forming 3D spheroids prone to spontaneous fusion. Supplementation of the standard culture medium with 0.25% HA significantly inhibited the fusion rates, preserving the shape and size uniformity of spheroids. The 3D cultures were assigned to two groups; a Cd44lo group had a tenfold decreased relative expression of Cd44 than another (Cd44hi) group. In addition, these two groups differed by expression levels of Sox2 transcription factor; the correlation analysis revealed a tight negative association for Cd44 and Sox2. Transcriptomic responses of spheroids to HA exposure also depended on Cd44 expression levels, from subtle in Cd44lo to more pronounced and specific in Cd44hi, involving cell cycle progression, PI3K/AKT/mTOR pathway activation, and multidrug resistance genes. The potential HA-induced increase in brain tumor 3D models’ resistance to anticancer drug therapy should be taken into account when designing preclinical studies using HA scaffold-based models. The property of HA to prevent the fusion of brain-derived spheroids can be employed in CNS regenerative medicine and experimental oncology to ensure the production of uniform, controllably fusing neurospheres when creating more accurate in vitro brain models.
Keywords: high-grade brain tumors; tissue strains; 3D culture; spheroids; hyaluronic acid; spheroid fusion high-grade brain tumors; tissue strains; 3D culture; spheroids; hyaluronic acid; spheroid fusion

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MDPI and ACS Style

Arutyunyan, I.; Soboleva, A.; Balchir, D.; Jumaniyazova, E.; Kudelkina, V.; Elchaninov, A.; Fatkhudinov, T. Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile. Biomolecules 2024, 14, 466. https://doi.org/10.3390/biom14040466

AMA Style

Arutyunyan I, Soboleva A, Balchir D, Jumaniyazova E, Kudelkina V, Elchaninov A, Fatkhudinov T. Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile. Biomolecules. 2024; 14(4):466. https://doi.org/10.3390/biom14040466

Chicago/Turabian Style

Arutyunyan, Irina, Anna Soboleva, Dorzhu Balchir, Enar Jumaniyazova, Vera Kudelkina, Andrey Elchaninov, and Timur Fatkhudinov. 2024. "Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile" Biomolecules 14, no. 4: 466. https://doi.org/10.3390/biom14040466

APA Style

Arutyunyan, I., Soboleva, A., Balchir, D., Jumaniyazova, E., Kudelkina, V., Elchaninov, A., & Fatkhudinov, T. (2024). Hyaluronic Acid Prevents Fusion of Brain Tumor-Derived Spheroids and Selectively Alters Their Gene Expression Profile. Biomolecules, 14(4), 466. https://doi.org/10.3390/biom14040466

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