IL-1α gene-transfected human melanoma cells increase tumor-cell adhesion to endothelial cells and their retention in the lung of nude mice
✍ Scribed by Renato G. S. Chirivi; Claudia Chiodoni; Piero Musiani; Angela Garofalo; Sergio Bernasconi; Mario P. Colombo; Raffaella Giavazzi
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 853 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The interleukin-I (Y (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-Ireceptor antagonist (IL-I ra) to the EC monolayer. Treatment of EC with colony-6-CM increased the expression of intercellularadhesion 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-CMinduced 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.