IL‐1α 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, Renato G. S., Chiodoni, Claudia, Musiani, Piero, Garofalo, Angela, Bernasconi, Sergio, Colombo, Mario P., Giavazzi, Raffaella
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 17-09-1996; Wiley-Liss
• Subjects: Animal tumors. Experimental tumors; Biological and medical sciences; Experimental respiratory system tumors; Medical sciences; Tumors; Lung disease; Animal model; Endothelial cell; Immunoglobulins; Intercellular adhesion molecule 1; Respiratory disease; E Selectin; Cytokine; Rodentia; Melanoma; Cell adhesion molecule; Interleukin 1α; Malignant tumor; Metastasis; Adhesion; Bronchopulmonary; Vertebrata; Mammalia; Transfection; Gene; Mouse; Animal; Established cell line; Bronchus disease
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19960917)67:6<856::AID-IJC16>3.0.CO;2-#

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.