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

Autor: Piero Musiani, Mario P. Colombo, Angela Garofalo, Claudia Chiodoni, Renato G. S. Chirivi, Raffaella Giavazzi, Sergio Bernasconi
Rok vydání: 1996
Předmět:
Zdroj: International Journal of Cancer. 67:856-863
ISSN: 1097-0215
0020-7136
Popis: The interleukin-1α (IL-I) 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-I, 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-I-receptor antagonist (IL-I ra) to the EC monolayer. Treatment of EC with colony-6-CM increased the expression of intercellular-adhesion molecule I (ICAM-I), vascular-cell-adhesion molecule I (VCAM-I) 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-I 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-I 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-I 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. © 1996 Wiley-Liss, Inc.
Databáze: OpenAIRE
Externí odkaz: