title: Transforming growth factor-beta enhances adhesion of melanoma cells to the endothelium in vitro.
abstract: Melanoma invasion requires migration through the vascular barrier. An early event in this process is the adhesion of metastatic cells to the endothelium. To elucidate the role of TGF-beta in the regulation of this process, human melanoma SK-MEL24 cells were labelled with [5'-(3)H]-thymidine and co-cultured with bovine pulmonary artery endothelial-cell monolayers. Radioactivity was assumed to be proportional to the number of SK-MEL24 cells bound to the endothelium. A low number of melanoma cells adhered to endothelial cells in a time-related manner. Pretreatment for 24 hr with 0.001 to 10 ng/ml TGF-beta1 or TGF-beta2 of both cell types enhanced melanoma-endothelium adhesion in a dose-dependent manner. Both melanoma and endothelial cells expressed RI- and RII-type TGF-beta receptors. The effect of TGF-beta was abolished by co-incubation with the proteoglycan decorin. Conditioned media from melanoma-endothelium co-cultures contained latent TGF-beta and failed to affect cell-cell adhesion. However, activation of TGF-beta by heating the medium or reducing the pH, increased melanoma-endothelium adhesion to an extent similar to that of the TGF-beta administered to the cultures. Zimography demonstrated that both cell types expressed urokinase-type plasminogen activator (uPA). Addition of plasminogen to the co-cultures, which was likely to be activated to plasmin by uPA, resulted in activation of TGF-beta and parallel stimulation of melanoma-endothelium adhesion. In conclusion, TGF-beta may enhance adhesion of melanoma cells to the endothelium, playing a relevant autocrine/paracrine role in the progression of invasive melanoma.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Teti
authors.forename: A
authors.initials: A
authors.lastname: De Giorgi
authors.forename: M T
authors.initials: MT
authors.lastname: Spinella
authors.forename: S
authors.initials: S
authors.lastname: Migliaccio
authors.forename: R
authors.initials: R
authors.lastname: Canipari
authors.forename: A
authors.initials: A
authors.lastname: Onetti Muda
authors.forename: T
authors.initials: T
authors.lastname: Faraggiana
mesh_terms: D030201:Activin Receptors, Type I; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D058575:Decorin; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D016326:Extracellular Matrix Proteins; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D010958:Plasminogen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D011509:Proteoglycans / Q000494:pharmacology; D011651:Pulmonary Artery; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D010958:Plasminogen; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator