multiple myeloma; matrix metalloproteinase-9; bone marrow; stromal cell; endothelial cell
Abstract :
[en] MM is a B-cell malignancy mainly characterized by monoclonal expansion of plasma cells in the BM, presence of paraprotein in serum and occurrence of osteolytic bone lesions. MMPs are a family of proteolytic enzymes that can contribute to cancer growth, invasion, angiogenesis, bone degradation and other processes important in the pathogenesis of MM. We investigated MMP-9 production in the 5T33MM murine model. Expression of MMP-9 protein in supernatant and cell extracts was analyzed by gelatin zymography. The in vitro, stroma-independent variant 5T33MMvt showed no protein expression of MMP-9 in contrast to in vivo growing MM cells, 5T33MMvv. However, when 5T33MMvt cells were injected into naive mice and isolated after tumor take (5T33MMvt-vv), they secreted a significant amount of MMP-9. These results were confirmed by specific staining of cytospins with an anti-MMP-9 antibody. The MMP-9 production by 5T33MMvt-vv cells disappeared when the cells were recultured in vitro. These data demonstrated that upregulation of MMP-9 occurs in vivo and that this process is dependent on the microenvironment. Cocultures of 5T33MMvt cells with STR10 BMECs induced MMP-9 in MM cells, as determined by both gelatin zymography and flow-cytometric analysis. In conclusion, our results demonstrate that MMP-9 production by MM cells is upregulated in vivo by the interaction of MM cells with BMECs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Van Valckenborgh, E.
Bakkus, M.
Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
St Pierre, Y.
Asosingh, K.
Van Riet, I.
Van Camp, B.
Vanderkerken, K.
Language :
English
Title :
Upregulation of matrix metalloproteinase-9 in murine 5T33 multiple myeloma cells by interaction with bone marrow endothelial cells
Publication date :
2002
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 1995;7:728-35.
Yu A, Hewitt R, Connor E, Stetler-Stevenson W. Matrix metalloproteinases. Drugs Aging 1997;11:229-44.
Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 1990;6:121-5.
Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999;13:781-92.
Olson MW, Gervasi DC, Mobashery S, Fridman R. Kinetic analysis of the binding of human matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. J Biol Chem 1997;272:29975-83.
Jackson C, Nguyen M, Arkell J, Sambrook P. Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis-targetting gelatinase A activation. Inflamm Res 2001;50:183-6.
Lindberg RL, De Groot CJ, Montagne L, Freitag P, van der Valk P, Kappos L, Leppert D. The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 2001;124:1743-53.
Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 2000;10:415-33.
Woessner J. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991;5:2145-54.
Kelly T, Borset M, Abe E, Gaddy-Kurten D, Sanderson R. Matrix metalloproteinases in multiple myeloma. Leuk Lymphoma 2000;37: 273-81.
Barillé S, Akhoundi C, Collette M, Mellerin M, Rapp M, Harousseau J, Bataille R, Amiot M. Metalloproteinases in multiple myeloma: production of matrix metalloproteinase-9 (MMP-9), activation of proMMP-2, and induction of MMP-1 by myeloma cells. Blood 1997; 90:1649-55.
Leppert D, Waubant E, Galardy R, Bunnett N, Hauser S. T cell gelatinases mediate basement membrane transmigration in vitro. J Immunol 1995;154:4379-89.
Garbisa S, Sartor L, Biggin S, Salvato B, Benelli R, Albini A. Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate. Cancer 2001;91:822-32.
Barillé S, Bataille R, Rapp M, Harousseau J, Amiot M. Production of metalloproteinase-7 (matrilysin) by human myeloma cells and its potential involvement in metalloproteinase-2 activation. J Immunol 1999;163:5723-8.
Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F, Dammacco F. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994;87:503-8.
Van Valckenborgh E, De Raeve H, Devy L, Blacher S, Munaut C, Noël A, Van Marck E, Van Riet I, Van Camp B, Vanderkerken K. Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo. Br J Cancer 2002;86:796-802.
Aoudjit F, Masure S, Opdenakker G, Potworowski E, St-Pierre Y. Gelatinase B (MMP-9), but not its inhibitor (TIMP-1), dictates the growth rate of experimental thymic lymphoma. Int J Cancer 1999;82: 743-7.
Moses MA. The regulation of neovascularization by matrix metalloproteinases and their inhibitors. Stem Cells 1997;15:180-9.
Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 2001;21:1104-17.
Taraboletti G, Gatto C, Innocenti S, Giavazzi R. Protease inhibitors in the control of tumor spread and angiogenesis. In: Skouteris GG, Nicholson GL. Intermolecular cross-talk in tumor metastasis. Amsterdam: IOS Press, 1999;257-62.
Radl J, De Glopper ED, Schuit HR, Zurcher C. Idiopathic paraproteinemia. II. Transplantation of the paraprotein-producing clone from old to young C57BL/KaLwRij mice. J Immunol 1979;122:609-13.
Radl J, Croese JW, Zurcher C, Van den Enden-Vieveen MH, De Leeuw AM. Animal model of human disease. Multiple myeloma. Am J Pathol 1988;132:593-7.
Vanderkerken K, Goes E, De Raeve H, Radl J, Van Camp B. Follow-up of bone lesions in an experimental multiple myeloma mouse model: description of an in vivo technique using radiography dedicated for mammography. Br J Cancer 1996;73:1463-5.
Vanderkerken K, De Raeve H, Goes E, Van Meirvenne S, Radl J, Van Riet I, Thielemans K, Van Camp B. Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/ KaLwRij mouse. Br J Cancer 1997;76:451-60.
Asosingh K, Radl J, Van Riet I, Van Camp B, Vanderkerken K. The 5TMM series: a useful in vivo mouse model of human multiple myeloma. Hematol J 2000;1:351-6.
Asosingh K, Günthert U, Bakkus M, De Raeve H, Goes E, Van Riet I, Van Camp B, Vanderkerken K. In vivo induction of insulin-like growth factor-I receptor and CD44v6 confers homing and adhesion to murine multiple myeloma cells. Cancer Res 2000;60:3096-104.
PE Applied Biosystems. ABI Prism 7700 sequence detecion system: relative quantitation of gene expression. User bulletin 2. Norwalk, CT: Perkin-Elmer, 1997.
Vacca A, Ribatti D, Iurlaro M, Albini A, Minischetti M, Bussolino F, Pellegrino A, Ria R, Rusnati M, Presta M, Vincenti V, Persico MG, et al. Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis. Int J Clin Lab Res 1998;28:55-68.
Dong Z, Nemeth JA, Cher ML, Palmer KC, Bright RC, Fridman R. Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells. Int J Cancer 2001;93:507-15.
Aoudjit F, Potworowski E, St-Pierre Y. Bi-directional induction of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 during T lymphoma/endothelial cell contact: implication of ICAM-1. J Immunol 1998;160:2967-73.
Vanderkerken K, De Greef C, Asosingh K, Arteta B, De Veerman M, Vande Broek I, Van Riet I, Kobayashi M, Smedsrod B, Van Camp B. Selective initial in vivo homing pattern of 5T2 multiple myeloma cells in the C57BL/KaLwRij mouse. Br J Cancer 2000;82:953-9.
Lane WJ, Dias S, Hattori K, Heissig B, Choy M, Rabbany SY, Wood J, Moore MA, Rafii S. Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood 2000;96:4152-9.
Mira E, Mañes S, Lacalle RA, Márquez G, Martínez-A C. Insulin-like growth factor I-triggered cell migration and invasion are mediated by matrix metalloproteinase-9. Endocrinology 1999;140:1657-64.
Vanderkerken K, Asosingh K, Braet F, Van Riet I, Van Camp B. Insulin-like growth factor-1 acts as a chemoattractant factor for 5T2 multiple myeloma cells. Blood 1999;93:235-41.
Kaushal G, Xiong X, Athota A, Rozypal T, Sanderson R, Kelly T. Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9. Br J Haematol 1999;104:365-73.
Vanderkerken K, Vande Broek I, Eizirik DL, Van Valckenborgh E, Asosingh K, Van Riet I, Van Camp B. Monocyte chemoattractant protein-1 (MCP-1), secreted by bone marrow endothelial cells, induces chemoattraction of 5T multiple myeloma cells. Clin Exp Metastasis 2002;19:87-90.
Stuve O, Chabot S, Jung SS, Williams G, Yong VW, Chemokine enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9. J Neuroimmunol 1997;80:38-46.
Kossakowska AE, Edwards DR, Prusinkiewicz C, Zhang MC, Guo D, Urbanski SJ, Grogan T, Marquez LA, Janowska-Wieczorek A. 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.
Shibata K, Kikkawa F, Nawa A, Suganuma N, Hamaguchi M. Fibronectin secretion from human peritoneal tissue induces Mr 92,000 type IV collagenase expression and invasion in ovarian cancer cell lines. Cancer Res 1997;57:5416-20.
Khan KM, Falcone DJ. Role of laminin in matrix induction of macrophage urokinase-type plasminogen activator and 92-kDa metalloproteinase expression. J Biol Chem 1997;272:8270-5.
Davies FE, Anderson KC. Novel therapeutic targets in multiple myeloma. Eur J Haematol 2000;64:359-67.
Uchiyama H, Barut B, Mohrbacher A, Chauhan D, Anderson K. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood 1993;82:3712-20.
Dalton WS. Insights into the pathogenesis of myeloma and potential new therapeutic approaches. Haematology 2001:169-77.
Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 1999;93: 1658-67.
Butcher E, Picker L. Lymphocyte homing and homeostasis. Science 1996;272:60-6.