PDGF-D/PDGF-ββ Receptor-Regulated Chemo-taxis of Malignant Mesothelioma Cells

Abstract

Background/Aims:Our earlier study suggested that platelet-derived growth factor (PDGF)- ββ receptor regulates chemotaxis of human malignant mesothelioma cells such as MSTO-211H, NCIH-2052, NCIH-2452, and NCIH-28 cells, but not non-malignant Met5A cells. The present study was designed to gain further insight into the PDGF-ββ receptor signals underlying the chemotaxis. Methods: PDGF-D secreted from cells, activation of Akt and ERK, and cell migration were monitored for cells with and without knocking-down PDGF-ββ receptor. Results: FBS significantly stimulated PDGF-D secretion from malignant mesothelioma cells, but not Met5A cells. PDGF-D activated Akt and ERK in both the non-malignant and malignant cells. PDGF-D significantly facilitated migration of malignant mesothelioma cells, but not Met5A cells, with the extent varying among the cell types. The facilitatory action of PDGF-D was clearly prevented by knocking-down PDGF-ββ receptor or inhibitors of PI3 kinase, PDK1, Akt, Rac1, ROCK, and MEK. Conclusion: The results of the present study indicate that PDGF-D promotes malignant mesothelioma cell chemotaxis through PDGF-ββ receptor signaling pathways along a PI3 kinase/PDK1/Akt/Rac1/ROCK axis and relevant to ERK activation.