IL-1alpha gene-transfected human melanoma cells increase tumor-cell adhesion to endothelial cells and their retention in the lung of nude mice.
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.
Chirivi
R G
RG
Laboratory of Biology and Treatment of Metastasis, Mario Negri Institute for Pharmacological Research, Milan, Italy.
Chiodoni
C
C
Musiani
P
P
Garofalo
A
A
Bernasconi
S
S
Colombo
M P
MP
Giavazzi
R
R
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004727:Endothelium / Q000473:pathology; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1