Biopolym. Cell. 2019; 35(6):417-426.
Structure and Function of Biopolymers
Fibroblasts modulate the tumor cell motility and their mTOR/S6K1 phosphorylation status in vitro
1Hotsuliak N. Ya., 1Kosach V. V., 1Tykhonkova I. O., 1Palchevskii S. S., 1Khoruzhenko A. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143


Aim. To determine the paracrine effect of cultured fibroblasts on the HeLa cell motility and mTOR/S6K1 phosphorylation status in the tumor cells in vitro. Background. High cancer cell locomotion is distinguishing feature of the malignant tumor. The mTOR/S6K1 signaling network is one of the key links in the intracellular mechanism of the regulation of cell migration. Also, the cancer cell motility is dependent on the tumor microenvironment but the ways of stroma influence on the cancer cell migration should be studied more precisely. Methods. Cell culture, Western blot analysis, scratch test, statistical analysis. Results. Application of the media conditioned by a highly confluent monolayer culture of primer human dermal fibroblasts or fibroblasts of NIH 3T3 line leads to a significant increase of the mTOR and S6K1 phosphorylation in HeLa cells. Besides, these conditioned media have an inhibitory effect on the locomotor properties of tumor cells quantitatively comparable with the effect of mTOR/S6K1 signaling inhibitor rapamycin. Moreover, the combination of rapamycin and fibroblast conditioned medium does not additionally change the cancer cell motility in comparison to the application of either rapamycin or fibroblast conditioned medium alone. Conclusion. The closest tumor microenvironment can significantly modulate the behavior of cancer cells and the efficiency of anticancer drugs. It should be taken into consideration when developing anti-cancer drugs.
Keywords: mTOR/S6K1 signaling network, tumor microenvironment, fibroblasts, cancer cell migration, HeLa tumor cell line


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