Abstract
The matrix metalloproteinases (MMPs) are important in tumour cell invasion and metastasis in many common cancers. However, relatively few studies have investigated the role of MMPs and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), in leukaemia cell invasion. This study examined two leukaemia cell lines, K562 and HL-60 and showed that the K562 cell line was four times more invasive than the HL-60 cell line. The expression of MMP-2, matrilysin (MMP-7), MMP-9, TIMP-1, TIMP-2 and TIMP-3 was analysed. Both cell lines produced similar amounts of MMP-2, MMP-9 and TIMP-2. The K562 cells expressed more TIMP-1 than the HL-60 cells and neither cell line expressed TIMP-3. Interestingly, only the K562 cells expressed matrilysin suggesting a potential role for matrilysin in leukaemia cell invasion. In vitro invasion assays performed in the presence of a matrilysin blocking antibody showed a 40% reduction in invasive ability. This data suggests that matrilysin plays an important role in leukaemia cell invasion.
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References
Sawyers CL, Denny CT, Witte ON. Leukemia and the disruption of normal haematopoiesis. Cell 1991; 64: 337–50.
Ries C, Loher F, Zang CB et al. Matrix metalloproteinase production by bone marrow mononuclear cells from normal individuals and patients with acute and chronic myeloid leukemia or myelodysplastic syndromes. Clin Cancer Res 1999; 5: 1115–24.
McDonnell S, Morgan M, Lynch CC. Role of matrix metalloproteinases in normal and disease processes. Biochem Soc Trans 1999; 27: 734–40.
Morgan M, Kniss D, McDonnell S. Expression of metalloproteinases and their inhibitors in human trophoblast continuous cell lines. Exp Cell Res 1998; 242: 18–26.
Yoshihara Y, Nakamura H, Obata K et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 2000; 59: 455–61.
Nelson AR, Fingleton B, Rothenburg ML et al. Matrix metalloproteinases: Biologic activity and clinical implications. J Clin Oncol 2000; 18: 1135–49.
Rudolph-Owen LA, Chan R, Muller WJ et al. The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. Cancer Res 1998; 58: 5500–6.
Hashimoto K, Kihira Y, Matuo Y et al. Expression of matrix metalloproteinase-7 and tissue inhibitor of metalloproteinase-1 in human prostate. J Urol 1998; 160: 1872–6.
Fingleton BM, Goss KJH, Crawford HC et al. Matrilysin in early stage intestinal tumorigenesis. APMIS 1999; 107: 102–10.
Wilson CL, Heppner KJ, Labosky PA et al. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci USA 1997; 94: 1402–7.
Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. BBA-Protein Struct M 2000; 1477: 267–83.
Stetler-Stevenson M, Mansoor A, Lim M et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells. Blood 1997; 89: 1708–15.
Janowska-Wieczorek A, Marquez LA, Matsuzaki A et al. Expression of matrix metalloproteinases (MMP-2 and-9) and tissue inhibitors of metalloproteinases (TIMP-1 and-2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells. Br J Haematol 1999; 105: 402–11.
Kossakowska AE, Edwards DR, Prusinkievicz C et al. Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin's lymphomas. Blood 1999; 94: 2080–9.
Shattuck-Brandt RL, Lamps LW, Goss KJH et al. Differential expression of matrilysin and cyclooxygenase-2 in intestinal and colorectal neoplasms. Mol Carc 1999; 24: 177–87.
Tapiovaara H, Alitalo R, Vaheri A. Plasminogen activation on tumor cell surface and its involvement in human leukemia. Adv Cancer Res 1996; 69: 101–33.
Devy L, Noel A, Baramova E et al. Production and activation of matrix metalloprotease-9 (MMP-9) by HL-60 promyelocytic leukemia cells. Biochem Biophys Res Commun 1997; 238: 842–6.
Moses MA, Wiederschain D, Loughlin KR et al. Increased incidence of matrix metalloproteinases in urine of cancer patients. Cancer Res 1998; 58: 1395–9.
Witty JP, McDonnell S, Newell KJ et al. Modulation of matrilysin levels in colon-carcinoma cell-lines affects tumorigenicity in vivo. Cancer Res 1994; 54: 4805–12.
Alvarez OA, Carmichael DF, Declerck YA. Inhibtion of collagenolytic activity and metastases of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. J Natl Cancer 1990; I 82: 589–95.
Gomez DE, Alonso DF, Yoshiji H et al. Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions. Eur J Cell Biol 1997; 74: 111–22.
Kahari VM, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med 1999; 31: 34–45.
Murate T, Yamashita K, Ohashi H et al. Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differectiation of erythropoietin-responsive mouse erythroleukemia cell line, ELMI-1-3, is closely related to its cell growth potentiating activity. Exp Hematol 1993; 21: 169–76.
Ritter LM, Garfield SH, Thorgiersson UP. Tissue inhibitor of metalloproteinases-1 (TIMP-1) binds to the cell surface and translocates to the nucleus of human MCF-7 breast carcinoma cells. Biochem Biophys Res Commun 1999; 257: 494–9.
Von Bredow DC, Cress AE, Howard EW et al. Activation of gelatinase-tissue-inhibitors-of-metalloproteinase complexes by matrilysin. Biochem J 1998; 331: 965–72.
Murphy G, Gavrilovic J. Proteolysis and cell migration: Creating a path? Curr Opin Cell Biol 1999; 11: 614–21.
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Lynch, C.C., Donnell, S.M. The role of matrilysin (MMP-7) in leukaemia cell invasion. Clin Exp Metastasis 18, 401–406 (2000). https://doi.org/10.1023/A:1010973808853
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DOI: https://doi.org/10.1023/A:1010973808853