Stromelysin-1 (MMP-3) is inducible in T lymphoma cells and accelerates the growth of lymphoid tumors in vivo.
Matrix metalloproteinase (MMP)-3 (stromelysin-1) degrades various components of the extracellular matrix as well as several non-matrix components; it has notably been shown to activate other MMPs relevant to cancer and metastasis, including MMP-9. MMP-3 gene expression in the tumor microenvironment could therefore contribute to cancer progression. Transcriptional regulation of MMP genes was often described to occur upon intercellular interactions, leading to overexpression of these genes by cancer and/or stromal cells. In the present work, we report that expression of MMP-3 in T lymphoma cells is transiently induced during specific intercellular contact with endothelial cells (EC). Moreover, mice injected with lymphoma cells expressing MMP-3 constitutively developed thymic lymphoma more rapidly than those injected with control lymphoma cells. We also found that overexpression of MMP-3 in lymphoma transfectants significantly improved their ability to migrate through the matrix when compared to cells transfected with the control vector. These results provide the first in vivo evidence that local expression of MMP-3 promotes lymphoma progression and indicate that MMP-3 expression is tightly regulated upon lymphoma cell/stromal cell interaction.
INRS-Institut Armand-Frappier, University of Québec, Laval, Que., Canada H7V 1B7.
Céline
C
Van Themsche
Edouard F
EF
Potworowski
Yves
Y
St-Pierre
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000201:enzymology; D004790:Enzyme Induction; D005260:Female; D015870:Gene Expression; D008223:Lymphoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D013953:Thymus Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
D019278:Matrix Metalloproteinase 3