Platelet-derived growth factor (PDGF) BB acts as a chemoattractant for human malignant mesothelioma cells via PDGF receptor beta-integrin alpha3beta1 interaction.
Platelet-derived growth factor BB (PDGF BB) and the PDGF receptor beta are expressed on mesothelioma cells, but their biological function has not yet been defined. In the present study we used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV or the nonmatrix adhesive molecule poly-L-lysine (PLL). Mesothelioma cells migrated towards PDGF BB at concentrations ranging from 0.78 to 12.5 ng/ml if matrix proteins were present as adhesive substrates. This migration was integrin dependent since the same cells failed to migrate if the adhesive interactions necessary for migration were provided by molecules other than integrins. Migration of mesothelioma cells on fibronectin, laminin or collagen-type IV in response to PDGF BB was inhibited if the cells were pretreated with blocking antibodies to alpha3beta1 integrin. These findings describe for the first time PDGF BB as a chemoattractant for malignant mesothelioma cells and that collaboration between PDGF receptor beta and integrin alpha3beta1 is necessary for the motile response of these cells to PDGF BB.
Klominek
J
J
Department of Lung Medicine, Karolinska Institute at Huddinge Hospital, Sweden. Julius.Klominek@impi.ki.se
Baskin
B
B
Hauzenberger
D
D
D002630:Chemotactic Factors / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000502:physiology*; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D002630:Chemotactic Factors; D039201:Integrin alpha3beta1; D016023:Integrins; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor