Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells.
Collagenase-3 (MMP-13) is characterized by an exceptionally wide substrate specificity and restricted expression. MMP-13 is 1 of the few MMPs primarily expressed by tumor cells in malignant tumors, e.g., squamous cell carcinomas and its expression correlates with their invasion capacity. In this work, we have constructed an expression vector and a recombinant adenovirus harboring human MMP-13 cDNA to investigate the role of MMP-13 in cancer cell invasion. Our results show that constitutive expression of MMP-13 by HT-1080 cells stably transfected with MMP-13 expression vector or transduced with MMP-13 adenovirus markedly increased their invasion both through type I collagen and reconstituted basement membrane (Matrigel) with no alterations in expression or activation of collagenase-1 (MMP-1), gelatinase-A (MMP-2), or gelatinase-B (MMP-9). The enhanced invasion capacity of MMP-13 expressing HT-1080 cells was dependent on MMP activity, as it was blocked by MMP inhibitor Batimastat (BB-94) and tissue inhibitor of metalloproteinases-3 (TIMP-3). Our data provide direct evidence for the role of MMP-13 as a potent invasion proteinase, which alone can enhance the ability of malignant cells to penetrate through both basement membrane and fibrillar collagen.
Ala-Aho
Risto
R
Centre for Biotechnology, University of Turku and Abo Akademi University, FIN-20520 Turku, Finland.
Johansson
Nina
N
Baker
Andrew H
AH
Kähäri
Veli-Matti
VM
D000256:Adenoviridae / Q000235:genetics; D001485:Basement Membrane / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D004338:Drug Combinations; D005354:Fibrosarcoma / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D024042:Collagen Type I; D018076:DNA, Complementary; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D013876:Thiophenes; D019717:Tissue Inhibitor of Metalloproteinase-3; C059485:matrigel; D010649:Phenylalanine; D003094:Collagen; C080985:batimastat; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1