IL-1alpha gene-transfected human melanoma cells increase tumor-cell adhesion to endothelial cells and their retention in the lung of nude mice

• Published in: International journal of cancer Vol. 67; no. 6; pp. 856 - 863
• Main Authors: Chirivi, R G, Chiodoni, C, Musiani, P, Garofalo, A, Bernasconi, S, Colombo, M P, Giavazzi, R
• Format: Journal Article
• Language: English
• Published: United States 17-09-1996
• Subjects: Animals; Cell Adhesion - genetics; Cell Adhesion Molecules - metabolism; E-Selectin - metabolism; Endothelium - pathology; Female; Humans; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-1 - genetics; Interleukin-1 - metabolism; Lung - pathology; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mice; Mice, Nude; Transfection; Tumor Cells, Cultured; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0020-7136

The interleukin-1alpha(IL-1) gene was introduced by retroviral gene transfer into the A375P human melanoma cell line. Two hygromycin-resistant colonies, colony 3 and colony 6, which respectively do not and do express and release IL-1, were selected on the basis of Northern blot and ELISA. Both colonies adhered to resting human endothelial cells (EC) to the same extent. Pre-treatment of EC for 6 hr with conditioned medium (CM) from colony 6, but not from colony 3, increased the adhesion of A375P melanoma and HT-29 colon-carcinoma cells to EC. This increase was blocked by adding interleukin-l-receptor antagonist (IL-1ra) to the EC monolayer. Treatment of EC with colony-6-CM increased the expression of intercellular-adhesion molecule I (ICAM-1), vascular-cell-adhesion molecule I (VCAM-1) and E-selectin. Co-cultivation of colony-6 but not colony-3 melanoma cells with EC caused time-dependent increased expression of these adhesion proteins, reflecting their kinetics of expression on EC. Treating the EC with monoclonal antibodies to VCAM-1 and E-selectin abolished the colony-6-CM-induced increase in adhesion respectively to A375P melanoma and HT-29 colon-carcinoma cells. In vivo, i.v. injection of colony-6 cells in nude mice increased the expression of VCAM-1 on lung microvascular EC. The retention of radiolabeled A375P melanoma cells in the lung was increased in nude mice primed with colony-6 cells, but not with colony-3 cells, injected 6 hr earlier. These results demonstrate that IL-1 produced constitutively by transformed A375P melanoma cells is functionally active, inducing adhesion molecules on EC that enhance their adhesiveness for tumor cells and increase tumor-cell retention in the lung of nude mice.