Endothelial cell-driven regulation of CD9 or motility-related protein-1 expression in multiple myeloma cells within the murine 5T33MM model and myeloma patients

• Published in: Leukemia Vol. 20; no. 10; pp. 1870 - 1879
• Main Authors: DE BRUYNE, E, ANDERSEN, T. L, DE RAEVE, H, VAN VAICKENBORGH, E, CAERS, J, VAN CAMP, B, DELAISSE, J.-M, VAN RIET, I, VANDERKERKEN, K
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing 01.10.2006; Nature Publishing Group
• Subjects: Animals; Antibodies; Antigens, CD - genetics; Antigens, CD - metabolism; Biological and medical sciences; Biology; Biopsy; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Cancer; CD9 antigen; Cell Communication; Cell Line, Tumor; Cell surface; Cells; Disease Models, Animal; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Flow Cytometry; Gene Expression Regulation, Neoplastic; Glycoproteins; Hematologic and hematopoietic diseases; Hematology; Human health sciences; Humans; Hématologie; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunohistochemistry; Immunology; Immunopathology; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Motility; Multiple myeloma; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Multiple Myeloma - physiopathology; Neoplasm Invasiveness; Polymerase chain reaction; Proteins; Sciences de la santé humaine; Solid tumors; Tetraspanin-29; Tumors; Up-Regulation; Belgium; Denmark; Human; Immunopathology; Animal model; Endothelial cell; endothelial cells; multiple myeloma; Hematology; Rodentia; B cell neoplasm; Malignant hemopathy; Lymphoid neoplasm; Myeloma; Vertebrata; Mammalia; Immunoglobulinopathy; Mouse; Lymphoproliferative syndrome; CD9; Tetraspanin
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/sj.leu.2404343

The cell surface expression of CD9, a glycoprotein of the tetraspanin family influencing several processes including cell motility and metastasis, inversely correlates with progression in several solid tumors. In the present work, we studied the expression and role of CD9 in multiple myeloma (MM) biology using the 5T33MM mouse model. The 5T33MMvitro cells were found to be CD9 negative. Injection of these cells in mice caused upregulation of CD9 expression, while reculturing them resulted in downregulation of CD9. Coculturing of CD9-negative 5T33MMvitro cells with BM endothelial cells (BMECs) resulted in a partial retrieval of CD9. Laser microdissection followed by real-time polymerase chain reaction and immunohistochemistry performed on bone sections of 5T33MMvivo diseased mice demonstrated strong local expression of CD9 on MM cells in contact with BMEC compared to MM cells further away. These findings were also confirmed by immunohistochemistry in MM patients. Neutralizing anti-CD9 antibodies inhibited transendothelial invasion of CD9-expressing human MM5.1 and murine 5T33MMvivo cells. In conclusion, we provide evidence that CD9 expression by the MM cells is upregulated in vivo by close interaction of the cells with BMEC and that CD9 is involved in transendothelial invasion, thus possibly mediating homing and/or spreading of the MM cells.