title: Anti-JAM-C therapy eliminates tumor engraftment in a xenograft model of mantle cell lymphoma.
abstract: Junctional adhesion molecule (JAM)-C is a member of the JAM family, expressed by a variety of different cell types, including human B lymphocytes and some B-cell lymphoma subtypes-in particular, mantle cell lymphoma (MCL). Treatment with anti-JAM-C pAbs reduces homing of human B cells to lymphoid organs in a NOD/SCID mouse model. In the present study, the role of JAM-C in the engraftment of human lymphoma B cells in mice was investigated. Administration of novel anti-JAM-C mAbs reduced tumor growth of JAM-C+MCL cells in bone marrow, spleen, liver, and lymph nodes of mice. Treatment with anti-JAM-C antibodies significantly reduced the proliferation of JAM-C-expressing lymphoma B cells. Moreover, the binding of anti-JAM-C antibodies inhibited the phosphorylation of ERK1/2, without affecting other signaling pathways. The results identify for the first time the intracellular MAPK cascade as the JAM-C-driven signaling pathway in JAM-C+B cells. Targeting JAM-C could constitute a new therapeutic strategy reducing lymphoma B-cell proliferation and their capacity to reach supportive lymphoid microenvironments.
authors.affiliation: Hematology Service, University Hospital, Geneva, Switzerland; and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Doñate
authors.affiliation: Hematology Service, University Hospital, Geneva, Switzerland; and.
authors.forename: Archana
authors.initials: A
authors.lastname: Vijaya Kumar
authors.affiliation: Department of Pathology and Immunology, University Medical Center, Geneva University, Switzerland beat.imhof@unige.ch.
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.affiliation: Hematology Service, University Hospital, Geneva, Switzerland; and thomas.matthes@hcuge.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Matthes
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006085:Graft Survival; D006801:Humans; D008221:Lymphoid Tissue / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology*; D020522:Lymphoma, Mantle-Cell / Q000276:immunology / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human; D009363:Neoplasm Proteins; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: B-cell homing; B-cell proliferation; mantle cell lymphoma treatment