Department of Transcription Factors, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Molecular Pharmacology and Radiology Department, Russian National Research Medical University, Moscow, Russia.
Cell Adh Migr. 2022 Dec;16(1):65-71. doi: 10.1080/19336918.2022.2072554.
The study's aim was to investigate the S100A4-mediated mechanisms of the regulation of tumor cell proliferation and migration in the human triple-positive breast carcinoma cell line MCF-7 (TPBC) and triple-negative breast carcinoma cell line MDA-MB-231 (TNBC). The proliferative activity of TNBC more than doubled during the incubation in the conditioned medium of TPBC. Extracellular S100A4 dose-dependently decreased the proliferative response of TPBC. TPBC negatively impacted the growth of TNBCs during their co-culturing. TPBC significantly decreased the migration activity of the TNBC cells while the S100A4 intracellular level in the TNBC was also decreasing. The decrease in the S100A4 intracellular level occurred due to the protein's monomeric form while the contribution of the dimeric form into the overall S100A4 concentration in TNBC cells increased 1.5-2-fold. The S100A4 pathway in the intercellular communication between TNBC and TPBCs also included the dexamethasone-sensitive mechanisms of S100A4 intra- and extracellular pools regulation.
本研究旨在探讨 S100A4 介导的人三阳性乳腺癌细胞系 MCF-7（TPBC）和三阴性乳腺癌细胞系 MDA-MB-231（TNBC）中肿瘤细胞增殖和迁移调节的机制。在 TPBC 的条件培养基中孵育时，TNBC 的增殖活性增加了一倍以上。细胞外 S100A4 浓度依赖性地降低了 TPBC 的增殖反应。在共培养过程中，TPBC 对 TNBC 的生长产生负面影响。TPBC 显著降低了 TNBC 细胞的迁移活性，同时 TNBC 细胞内 S100A4 水平也降低。S100A4 细胞内水平的降低是由于其单体形式，而二聚体形式在 TNBC 细胞中总 S100A4 浓度中的贡献增加了 1.5-2 倍。TNBC 和 TPBC 之间细胞间通讯中的 S100A4 途径还包括地塞米松敏感的 S100A4 细胞内外池调节机制。
