Fibroblasts modulate the tumor cell motility and their mTOR/S6K1 phosphorylation status in vitro

Abstract

To determine the paracrine effect of cultured fibroblasts on HeLa cell motility and mTOR/ S6K1 phosphorylation status in vitro. Background. High cancer cell motility is a feature of the malignant tumor. The mTOR/S6K1 signaling network is one of the key links in regulation of cell migration. The cancer cell motility is also dependent on the tumor microenvironment but the effect of stroma on cancer cell migration is insufficiently studied. 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 NIH 3T3 fibroblasts leads to a significant increase of the mTOR and S6K1 phosphorylation in HeLa cells. These conditioned media also have an inhibitory effect on the motility of tumor cells similar to that 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 rapamycin or fibroblast conditioned medium alone. Conclusion. The tumor microenvironment can significantly modulate the behavior of cancer cells and the efficiency of anticancer drugs. This should be taken into consideration when developing anticancer drugs.