Stromelysin-2 (matrix metalloproteinase 10) is inducible in lymphoma cells and accelerates the growth of lymphoid tumors in vivo.
Matrix metalloproteinase (MMP) 10 (stromelysin-2) is known to degrade various components of the extracellular matrix; however, the signals that regulate its expression and its role in lymphoma growth remain unknown. In the present work, we report the up-regulated expression of MMP10 in T lymphoma cells following contact with endothelial cells. The induction of MMP10 was found to be dependent on the specific interaction between LFA-1 and ICAM-1, which play a central role in regulating the expression of genes involved in the rate-limiting steps of lymphoma development. MMP10, but not MMP3 (stromelysin-1), was also up-regulated in human B lymphoma cells following exposure to IL-4, IL-6, and IL-13, but not to IL-1. To gain further insight into the role of MMP10 in lymphoma development, we generated lymphoma cell lines constitutively expressing high levels of MMP10 and studied these cells for their ability to form thymic lymphoma in vivo. Mice injected with lymphoma cells constitutively expressing MMP10 developed thymic lymphoma more rapidly than those injected with control lymphoma cells. These results provide the first in vivo evidence that overexpression of MMP10 promotes tumor development, and indicate that MMP10 induction is an important pathway activated not only upon ICAM-1/LFA-1-mediated intercellular contact, but also following activation of tumor cells with inflammatory cytokines.
Van Themsche
Céline
C
Institut National de la Recherche Scientifique-Institut Armand-Frappier, University of Québec, Laval, Canada.
Alain
Tommy
T
Kossakowska
Anna E
AE
Urbanski
Stefan
S
Potworowski
Edouard F
EF
St-Pierre
Yves
Y
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology; D004790:Enzyme Induction / Q000235:genetics / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006390:Hemangioendothelioma / Q000201:enzymology / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10