Infiltrative capacity of T leukemia cell lines: a distinct functional property coupled to expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1).
Infiltrative capacity was found to distinguish separate T leukemia cell lines. Of seven T-cell lines four exhibited capacity to infiltrate Matrigel. Analysis of infiltration was performed at the single-cell level throughout the Matrigel using a depth meter. Further, we examined differences in migration capacity and metalloproteinase production between infiltrating and non-infiltrating T-cell lines. The capacity to infiltrate was not directly correlated to the capacity to adhere to the Matrigel or to migrate on/to extracellular matrix components. It is concluded that infiltration capacity does not simply reflect capacity to migrate but represents a distinct functional property. The production of metalloproteinases and their inhibitors by the separate T-cell lines was analyzed using rt PCR, biosynthetic labelling, zymography, immunoprecipitation and ELISA. All T-cell lines with capacity to infiltrate produced matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) while non-infiltrating cell lines did not express MMP-9. Expression of MMP-1, 2, 3, 10, 14 and 17 showed no correlation to capacity to infiltrate. Analysis of infiltration in the presence of a metalloprotease inhibitor showed an increased number of cells within the gel. This enhancement of infiltration suggests that the function of MMPs and/or their inhibitors in lymphocyte infiltration is more complex than previously thought.
Department of Clinical Immunology, University of Umeå, Sweden.
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Ivanoff
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Ivanoff
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Hultenby
K G
KG
Sundqvist
D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002465:Cell Movement / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D004792:Enzyme Precursors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids; D007797:Laminin; D015458:Leukemia, T-Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D017254:Leukemic Infiltration / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D004792:Enzyme Precursors; D005353:Fibronectins; D006877:Hydroxamic Acids; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011509:Proteoglycans; D012333:RNA, Messenger; C097661:Ro 31-9790; D019715:Tissue Inhibitor of Metalloproteinase-1; C059485:matrigel; D005780:Gelatin; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9