title: PDGF-D/PDGF-ββ receptor-regulated chemotaxis of malignant mesothelioma cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Okada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Akinobu
authors.initials: A
authors.lastname: Gotoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002633:Chemotaxis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034622:RNA Interference; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D008222:Lymphokines; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta; D020830:rac1 GTP-Binding Protein; D054460:rho-Associated Kinases; C427493:PDGFD protein, human; C000631429:PDK1 protein, human