REVIEW: Molecular Mechanisms of Tumor Cell Stemness Modulation during Formation of Spheroids

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Aleksei S. Ponomarev¹, Zarema E. Gilazieva¹, Valeriya V. Solovyova¹, and Albert A. Rizvanov^1,a*

¹Kazan (Volga Region) Federal University, 420008 Kazan, Republic of Tatarstan, Russia

^* To whom correspondence should be addressed.

Received January 31, 2023; Revised May 30, 2023; Accepted June 7, 2023

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Cancer stem cells (CSCs), their properties and interaction with microenvironment are of interest in modern medicine and biology. There are many studies on the emergence of CSCs and their involvement in tumor pathogenesis. The most important property inherent to CSCs is their stemness. Stemness combines ability of the cell to maintain its pluripotency, give rise to differentiated cells, and interact with environment to maintain a balance between dormancy, proliferation, and regeneration. While adult stem cells exhibit these properties by participating in tissue homeostasis, CSCs behave as their malignant equivalents. High tumor resistance to therapy, ability to differentiate, activate angiogenesis and metastasis arise precisely due to the stemness of CSCs. These cells can be used as a target for therapy of different types of cancer. Laboratory models are needed to study cancer biology and find new therapeutic strategies. A promising direction is three-dimensional tumor models or spheroids. Such models exhibit properties resembling stemness in a natural tumor. By modifying spheroids, it becomes possible to investigate the effect of therapy on CSCs, thus contributing to the development of anti-tumor drug test systems. The review examines the niche of CSCs, the possibility of their study using three-dimensional spheroids, and existing markers for assessing stemness of CSCs.

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KEY WORDS: cancer stem cells, stem cells, malignant neoplasms, tumor spheroids, tumor microenvironment, transcription factors, test system

DOI: 10.1134/S0006297923070106

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