Deregulated human glioma cell motility: inhibitory effect of somatostatin.
Malignant gliomas are highly invasive tumors which are lethal despite aggressive therapy. The motility behavior of two human glioma cell lines i.e. T98G and U87-MG cells was analysed. The glioma cells showed a high degree of basal motility (especially U87-MG cells) that may be related to the considerable local invasiveness of such tumours even in the absence of exogenous factors. The two cell lines responded equally well to platelet-derived growth factor (PDGF) as chemoattractant factor. The phosphatidylinositol 3-kinase (PI3-K) signaling, but not the extracellular signal-related kinase (ERK) signaling, was strongly involved in the PDGF-stimulated glioma cell motility. Somatostatin was capable of inhibiting the migration in both glioma cell lines without affecting crucial targets for motility control like PI3-K and Rac activity. These data suggest that somatostatin, by interfering with a target further downstream to Rac, negatively affects glioma cell motility, and may thus offer a pharmacological approach to controlling the deregulated motility of these aggressive tumoral cells.
Cattaneo
Maria Grazia
MG
Department of Pharmacology, School of Medicine, University of Milano, Via Vanvitelli 32, 20129 Milano, Italy.
Gentilini
Davide
D
Vicentini
Lucia Maria
LM
D002070:Butadienes / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002630:Chemotactic Factors / Q000494:pharmacology; D002867:Chromones / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000378:metabolism; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D002070:Butadienes; D002630:Chemotactic Factors; D002867:Chromones; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D006728:Hormones; D009025:Morpholines; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D013004:Somatostatin; D020744:rac GTP-Binding Proteins; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one