Transforming growth factor-beta enhances adhesion of melanoma cells to the endothelium in vitro
| Autor: | A, Teti, A, De Giorgi, M T, Spinella, S, Migliaccio, R, Canipari, A, Onetti Muda, T, Faraggiana |
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| Rok vydání: | 1997 |
| Předmět: |
Extracellular Matrix Proteins
Skin Neoplasms Receptor Transforming Growth Factor-beta Type I Receptor Transforming Growth Factor-beta Type II Plasminogen Protein Serine-Threonine Kinases Pulmonary Artery Urokinase-Type Plasminogen Activator Coculture Techniques Recombinant Proteins Kinetics Transforming Growth Factor beta Cell Adhesion Tumor Cells Cultured Animals Humans Cattle Proteoglycans Endothelium Vascular Fibrinolysin Decorin Activin Receptors Type I Melanoma Receptors Transforming Growth Factor beta Cells Cultured |
| Zdroj: | International journal of cancer. 72(6) |
| ISSN: | 0020-7136 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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