The Mechanisms of Stimulation of Migration and Invasion of Tumor Cells by Extracellular Heat Shock Protein 90 (eHsp90) in vitro

Extracellular heat shock protein 90 (eHsp90) plays an important role in cell motility, invasion, and metastasis of tumor cells. eHsp90 stimulates migration and invasion of cells via interaction with surface receptors, which is accompanied by the activation of multiple cell motility-related signaling pathways. In addition, еHsp90 promotes cell invasion by the activation of extracellular matrix metalloproteinases. The role of different receptors, intracellular signaling pathways, and matrix metalloproteinases in the еHsp90-dependent migration and invasion of different types of cells has been investigated insufficiently. In this study, we demonstrated that HER2 is involved in the еHsp90-mediated stimulation of migration and invasion of human glioblastoma A-172 and fibrosarcoma HT1080 cells in vitro. eHsp90-induced migration and invasion of cells are accompanied by the activation of ERK1/2-, IKK/NF-κB-, FAK-, ROCK1- and Src-mediated signaling pathways and by the limited activation of JNK, while the p38-mediated signaling cascade is not activated. eHsp90 also stimulates PI3K-Akt signaling pathway in А-172 cells, while in НТ1080 cells Akt is activated regardless of PI3K. It has been established that matrix metalloproteinases are involved in the eHsp90-dependent stimulation of invasion of А-172 and НТ1080 cells in vitro.