Bone marrow endothelial cells increase the invasiveness of human multiple myeloma cells through upregulation of MMP-9: evidence for a role of hepatocyte growth factor
The migration of multiple myeloma (MM) cells from the circulation into the bone marrow (BM) implicates that they must have the capacity to cross the BM endothelium including the subendothelial basement membrane. In this study, human CD138+ MM cells were immunomagnetically isolated from BM samples of...
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Published in | Leukemia Vol. 18; no. 5; pp. 976 - 982 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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London
Nature Publishing
01.05.2004
Nature Publishing Group |
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Abstract | The migration of multiple myeloma (MM) cells from the circulation into the bone marrow (BM) implicates that they must have the capacity to cross the BM endothelium including the subendothelial basement membrane. In this study, human CD138+ MM cells were immunomagnetically isolated from BM samples of MM patients and their invasion through Matrigel, that is, a reconstituted basement membrane, was determined. We demonstrated that primary MM cells have the capacity to transmigrate through basement membrane and that this invasiveness was considerably increased when assessed on Matrigel filters coated with BM endothelial cells (EC) (4LHBMEC line) (transendothelial invasion). The isolated MM cells were shown by zymography to secrete matrix metalloproteinase (MMP)-9 and anti-MMP-9 antibodies inhibited transendothelial invasion, indicating that MMP-9 is involved in this process. BM EC were found to increase the MMP-9 secretion in MM cells, indicating that EC enhance MM cell invasion through stimulation of MMP-9 secretion. BM EC were found to produce hepatocyte growth factor (HGF), and this cytokine also stimulated MMP-9 secretion in MM cells, while anti-HGF antibodies significantly inhibited EC-stimulated MM cell invasion. In summary, our findings provide evidence that MM cell-BM EC interactions enhance the invasion of human MM cells through stimulation of MMP-9 secretion. |
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AbstractList | The migration of multiple myeloma (MM) cells from the circulation into the bone marrow (BM) implicates that they must have the capacity to cross the BM endothelium including the subendothelial basement membrane. In this study, human CD138 super(+) MM cells were immunomagnetically isolated from BM samples of MM patients and their invasion through Matrigel, that is, a reconstituted basement membrane, was determined. We demonstrated that primary MM cells have the capacity to transmigrate through basement membrane and that this invasiveness was considerably increased when assessed on Matrigel filters coated with BM endothelial cells (EC) (4LHBMEC line) (transendothelial invasion). The isolated MM cells were shown by zymography to secrete matrix metalloproteinase (MMP)-9 and anti-MMP-9 antibodies inhibited transendothelial invasion, indicating that MMP-9 is involved in this process. BM EC were found to increase the MMP-9 secretion in MM cells, indicating that EC enhance MM cell invasion through stimulation of MMP-9 secretion. BM EC were found to produce hepatocyte growth factor (HGF), and this cytokine also stimulated MMP-9 secretion in MM cells, while anti-HGF antibodies significantly inhibited EC-stimulated MM cell invasion. In summary, our findings provide evidence that MM cell-BM EC interactions enhance the invasion of human MM cells through stimulation of MMP-9 secretion. The migration of multiple myeloma (MM) cells from the circulation into the bone marrow (BM) implicates that they must have the capacity to cross the BM endothelium including the subendothelial basement membrane. In this study, human CD138+ MM cells were immunomagnetically isolated from BM samples of MM patients and their invasion through Matrigel, that is, a reconstituted basement membrane, was determined. We demonstrated that primary MM cells have the capacity to transmigrate through basement membrane and that this invasiveness was considerably increased when assessed on Matrigel filters coated with BM endothelial cells (EC) (4LHBMEC line) (transendothelial invasion). The isolated MM cells were shown by zymography to secrete matrix metalloproteinase (MMP)-9 and anti-MMP-9 antibodies inhibited transendothelial invasion, indicating that MMP-9 is involved in this process. BM EC were found to increase the MMP-9 secretion in MM cells, indicating that EC enhance MM cell invasion through stimulation of MMP-9 secretion. BM EC were found to produce hepatocyte growth factor (HGF), and this cytokine also stimulated MMP-9 secretion in MM cells, while anti-HGF antibodies significantly inhibited EC-stimulated MM cell invasion. In summary, our findings provide evidence that MM cell-BM EC interactions enhance the invasion of human MM cells through stimulation of MMP-9 secretion. |
Audience | Academic |
Author | ASOSINGH, K FACON, T VANDE BROEK, I VAN CAMP, B ALLEGAERT, V VANDERKERKEN, K LELEU, X VAN RIET, I |
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Keywords | Human Immunopathology Endothelial cell multiple myeloma Hematology Enzyme Hepatocyte growth factor Metalloendopeptidases transendothelial invasion Malignant hemopathy Myeloma Gelatinase B Invasion Endothelium Peptidases Immunoglobulinopathy Lymphoproliferative syndrome Bone marrow Hydrolases Homing phenomenon homing MMP-9 |
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Snippet | The migration of multiple myeloma (MM) cells from the circulation into the bone marrow (BM) implicates that they must have the capacity to cross the BM... |
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SubjectTerms | Angiogenesis Antibodies Basements Biological and medical sciences Blood vessels Bone marrow Bone Marrow Cells - physiology Cells Cells, Cultured Cytokines Endothelial cells Endothelial Cells - physiology Endothelium Gelatinase B Growth factors Hematologic and hematopoietic diseases Hematology Hepatocyte growth factor Hepatocyte Growth Factor - physiology Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunology Immunopathology Invasiveness Kinases Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphocytes Matrix metalloproteinase Matrix Metalloproteinase 9 - physiology Matrix metalloproteinases Medical sciences Membranes Metalloproteinase Multiple myeloma Multiple Myeloma - enzymology Multiple Myeloma - pathology Neoplasm Invasiveness Pathogenesis Stimulation Up-Regulation |
Title | Bone marrow endothelial cells increase the invasiveness of human multiple myeloma cells through upregulation of MMP-9: evidence for a role of hepatocyte growth factor |
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