Influence of high-molecular hyaluronic acid on MCF-7 breast cancer stem cells

Abstract

In recent years, more and more data have been accumulating on the high radio- and chemo-resistance of tumor stem cells (CSCs), confirming the assumption that these cells play an important role in the recurrence of the tumor process in some cancer patients. Therefore it is of considerable interest to elucidate the patterns and mechanisms of the formation of the CSC pool under the influence of various factors, including one of the main components of the extracellular matrix, hyaluronic acid (HA). The purpose of the study was to elucidate the effects of HA with a molecular weight of (1-3) x 106 Dа on the amount of CSCs in MCF-7 breast cancer cell culture in vitro. Material and methods. Using the MTT test, the viability of MCF-7 cancer cells was determined after incubation with HA at a concentration of 0.3-5.0 mg/ml. Using flow cytometry, we evaluated the change in the relative and absolute amount of CSCs under the influence of HA (0.6 mg/ml). CSCs were detected by CD44+CD24-/low immunophenotype, as well as by their ability to efficiently efflux Hoechst 33342 fluorescent dye from cells and form so-called side population (SP). Results. Viability of cancer cells in the general population decreased with increasing concentration of HA (R=-0.94, p=0.006). At the same time the incubation of cells with HA led to an increase in both the relative and absolute amounts of CSCs (SP) compared with the control. Thus, the relative number of SP cells increased by 2.0 times (p = 0.002), CD44 + CD24- / low cells - by 6.1 times (p = 0.005). The absolute number of these cells changed to a lesser extent compared to the control: the increase was 1.6 (p = 0.004) and 2.9 times (p = 0.02), respectively. Conclusion. Thus, the effect of high-molecular weight HA on breast cancer cells of MCF-7 line leads to an increase in amount of CSCs, while the viability of non-stem cancer cells decreases under the same conditions.