Bi-directional induction of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 during T lymphoma/endothelial cell contact: implication of ICAM-1.
The mechanisms that lead to the expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMPs) during the invasive process of normal and transformed T cells remain largely unknown. Since vascular cells form a dynamic tissue capable of responding to local stimuli and activating cells through the expression of cytokine receptors and specific cell adhesion molecules, we hypothesized that the firm adhesion of T lymphoma cells to endothelial cells is a critical event in the local production of MMP and TIMP. In the present work, we show that adhesion of lymphoma cells to endothelial cells induced a transient and reciprocal de novo expression of MMP-9 mRNA and enzymatic activity by both cell types. Up-regulation of MMP-9 in T lymphoma cells was concomitant to that of TIMP-1, and required direct contact with endothelial cells. Induction of MMP-9, but not of TIMP-1, was blocked by anti-LFA-1 and anti-intercellular adhesion molecule-1 Abs, indicating that induction of MMP-9 and TIMP-1 in lymphoma cells required direct, yet distinct, intercellular contact. In contrast, the induction of MMP-9 in endothelial cells by T lymphoma cells did not necessitate direct contact and could be achieved by exposure to IL-1 and TNF, or to the supernatant of T lymphoma cell culture. Together, these results demonstrate that firm adhesion of T lymphoma cells to endothelial cells participates in the production of MMP-9 in both cell types through bi-directional signaling pathways, and identify intercellular adhesion molecule-1/LFA-1 as a key interaction in the up-regulation of MMP-9 in T lymphoma cells.
Aoudjit
F
F
Immunology Research Center, Institut Armand-Frappier, Université du Québec, Laval, Canada.
Potworowski
E F
EF
St-Pierre
Y
Y
D000818:Animals; D002450:Cell Communication; D018920:Coculture Techniques; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology*; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016399:Lymphoma, T-Cell / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016169:Lymphocyte Function-Associated Antigen-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1; D017364:Collagenases; D020780:Matrix Metalloproteinase 9