HYALURONIC ACID IN THE CELL CYCLE OF TUMOR CELLS

DOI: https://doi.org/10.29296/24999490-2020-05-02

V.N. Khabarov(1), N.N. Belushkina(2), M.A. Paltsev(2), I.M. Kvetnoy(3, 4) 1-Research Center of hyaluronic acid, Komsomolsky Ave. 38/16, Moscow, 119146, Russian Federation; 2-Lomonosov Moscow State University, Leninskie gory, 1/12, Moscow, 119991, Russian Federation; 3-Saint-Petersburg State Research Institute of Phthisiopulmonology, Ligovskij avenue, 2–4, Saint-Petersburg, 191036, Russian Federation; 4-Saint-Petersburg State University, Universitetskaia emb., 7–9, Saint-Petersburg, 199034, Russian Federation E-mail: [email protected]

The review considers the role of hyaluronic acid (HA), primarily low-molecular-weight fractions of HA, in the regulation of the cell cycle of tumor cells. The formation of a pool of low-molecular weight HA molecules is due to the high activity of hyaluronidases, absolutely prerequisite for the development of a tumor in the case of intensive cell division. There was also a high level of HA in tumor cells due to the increased activity of hyaluronate synthases HAS1, 2, 3. HA, interacting with the CD44 receptor, alter the functional activity of cytokines, regulatory proteins, and gene groups. This contributes to the continuous proliferation of the tumor cells and strengthens the processes associated with cell invasion and migration. The formation of a complex of receptors around CD44 plays an important role in the continuous activation of the cycle responses in tumor cells. In most types of normal cells, the activity of CD44 receptor genes is suppressed by the p53 protein. The degeneration of a normal cell into a tumor cell is usually associated with deletions and mutations of the p53 protein gene, resulting in high activity of the CD44 receptor. In the case of the native p53 protein gene, activation of the CD44 receptor gene is carried out due to a high concentration of IL-6 cytokine, which activates and supports a cascade of CD44 gene activation responses. As a result, there is a constant activity of a number of major regulatory proteins: C-Myc, c-Ras, c-Src, K-Ras, Akt, ERK, β-catenin, STAT3, etc., characteristic of tumor cells.`
Keywords: 
hyaluronic acid, cell cycle, CD44, low molecular weight fraction of hyaluronic acid, tumor cell
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