title: Multiple myeloma in a murine syngeneic model:modulation of growth and angiogenesis by a monoclonal antibody to kininogen.
abstract: Multiple myeloma (MM), a B-cell malignancy characterized by proliferation of monoclonal plasma cells remains incurable. Murine plasma cell tumors share common features with human MM. We used two cell lines (B38 and C11C1) derived from P3X63Ag8 myeloma cells. The new cell lines were implanted subcutaneously in the strain of origin (Balb/c mice) and used as a model to monitor the effects of C11C1 monoclonal antibody (mAb) to kininogen (HK). We assessed their behavior by intraperitoneal and subcutaneous implantation, by implanting them together and by treating B38-MM with purified mAb C11C1. We evaluated growth, microvascular density (MVD), and cellular expression of urokinase-type plasminogen activator-receptor (uPAR), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), bradykinin-1 receptor (B1R), bradykinin-2 receptor (B2R) and HK. We found that both MM-cell-lines are uPAR positive, that mAb C11C1 inhibits its own tumor growth in vivo, slows down B38-MM growth rate when both MM are implanted together and when mAb C11C1 is injected intraperitoneally. MAb C11C1-treated-MM showed decreased MVD and HK binding in vivo without FGF-2, B1R or B2R expression changes. We propose that the B38-extramedullary-myeloma-model is a useful tool to study the interactions of this hematopoietic tumor and its environment and that mAb C11C1 may improve the efficacy of conventional MM treatment with minimal side effects.
authors.affiliation: The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Irma M
authors.initials: IM
authors.lastname: Sainz
authors.forename: Irma
authors.initials: I
authors.lastname: Isordia-Salas
authors.forename: Ricardo G
authors.initials: RG
authors.lastname: Espinola
authors.forename: Walter K
authors.initials: WK
authors.lastname: Long
authors.forename: Robin A
authors.initials: RA
authors.lastname: Pixley
authors.forename: Robert W
authors.initials: RW
authors.lastname: Colman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D045744:Cell Line, Tumor / Q000473:pathology / Q000637:transplantation; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007704:Kininogens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects; D009101:Multiple Myeloma / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000628:therapy*; D043783:Receptor, Bradykinin B1 / Q000096:biosynthesis / Q000235:genetics; D043782:Receptor, Bradykinin B2 / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D040521:Subcutaneous Tissue; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D007704:Kininogens; D009363:Neoplasm Proteins; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2