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IL‐1α gene‐transfected human melanoma cells increase tumor‐cell adhesion to endothelial cells and their retention in the lung of nude mice
Author(s) -
Chirivi Renato G. S.,
Chiodoni Claudia,
Musiani Piero,
Garofalo Angela,
Bernasconi Sergio,
Colombo Mario P.,
Giavazzi Raffaella
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960917)67:6<856::aid-ijc16>3.0.co;2-#
Subject(s) - transfection , cancer research , endothelial stem cell , tumor cells , cell adhesion , melanoma , biology , cell , cell culture , ratón , lung , pathology , microbiology and biotechnology , immunology , medicine , in vitro , genetics
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.