Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C
| Autor: | Patricia Ropraz, Thomas Alexander Mckee, Carmen Donate, Thomas Matthes, Nicolas Fischer, Beat A. Imhof, Christiane Ody, Sylvie Ruault-Jungblut |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Pathology Lymphoma B-Cell/immunology Mice SCID ddc:616.07 Mice 0302 clinical medicine Bone Marrow Cell Movement Mice Inbred NOD B-cell lymphoma ddc:616 0303 health sciences B-Lymphocytes B-Lymphocytes/immunology Adoptive Transfer humanities 3. Good health Lymphatic system medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis cardiovascular system Spleen/immunology medicine.medical_specialty Lymphoma B-Cell education Lymph Nodes/immunology Biology 03 medical and health sciences Bone Marrow/immunology medicine Lymph node stromal cell Animals Humans Lymphocyte homing receptor 030304 developmental biology Cell Adhesion Molecules/immunology/metabolism/physiology fungi medicine.disease Lymphoma B-1 cell Cell Movement/immunology Cancer research Bone marrow Lymph Nodes Cell Adhesion Molecules Spleen Homing (hematopoietic) |
| Zdroj: | Cancer Research, Vol. 73, No 2 (2013) pp. 640-51 Cancer research |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone–derived (JAM-C–positive) and germinal center–derived (JAM-C–negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C–expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C–expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen. Cancer Res; 73(2); 640–51. ©2012 AACR. |
| Databáze: | OpenAIRE |
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