Transforming growth factor-β enhances adhesion of melanoma cells to the endothelium in vitro

✍ Scribed by Anna Teti; Annamaria De Giorgi; Maria T. Spinella; Silvia Migliaccio; Rita Canipari; Andrea Onetti Muda; Tullio Faraggiana

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 368 KB
• Volume: 72
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970917)72:6<1013::aid-ijc16>3.0.co;2-5

✦ Synopsis

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-␤ in the regulation of this process, human melanoma SK-MEL24 cells were labelled with [5Ј-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-␤ 1 or TGF-␤ 2 of both cell types enhanced melanoma-endothelium adhesion in a dose-dependent manner. Both melanoma and endothelial cells expressed RI-and RII-type TGF-␤ receptors. The effect of TGF-␤ was abolished by co-incubation with the proteoglycan decorin. Conditioned media from melanoma-endothelium co-cultures contained latent TGF-␤ and failed to affect cell-cell adhesion. However, activation of TGF-␤ by heating the medium or reducing the pH, increased melanoma-endothelium adhesion to an extent similar to that of the TGF-␤ 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-␤ and parallel stimulation of melanoma-endothelium adhesion. In conclusion, TGF-␤ may enhance adhesion of melanoma cells to the endothelium, playing a relevant autocrine/ paracrine role in the progression of invasive melanoma.