title: Alpha(v)beta(3) integrin engagement enhances cell invasiveness in human multiple myeloma.
abstract: OBJECTIVE
  In multiple myeloma (MM), the mechanisms used by plasma cells to invade locally and metastasize are thought to be similar to those developed by solid tumors and include cell proliferation and secretion of extracellular matrix (ECM) degrading enzymes following adhesion to ECM proteins. We studied these mechanisms in fresh bone marrow plasma cells of patients with MM after adhesion to the ECM proteins vitronectin (VN) and fibronectin (FN).
  
  
  METHODS
  The ability of bone marrow plasma cells to adhere to VN and FN and the consequent formation of focal adhesion plaques on the cell surface, their composition and phosphorylation of several signal transduction proteins, cell proliferation and secretion of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and urokinase-type plasminogen activator (uPA) were studied.
  
  
  RESULTS
  Plasma cells adhered to immobilized VN and FN. Adhesion was fully prevented by neutralizing anti-avb3 integrin antibody. Integrin engagement caused aggregation of the plaques, which contained the b3 integrin subunit, some cytoskeletal proteins, tyrosine kinases, the Grb-2 adapter protein, and mitogen-activated protein (MAP) kinase. Free and immobilized VN and FN stimulated cell proliferation and the production and the release of uPA, and increased the release of the activated forms of MMP-2 and MMP-9 in an avb3 integrin-dependent manner.
  
  
  CONCLUSIONS
  This ability of myeloma plasma cells to interact with VN and FN via avb3 integrin engagement suggests a novel mechanism for their invasion and spreading, since this interaction allows them to adhere to the substratum and enhances their proliferation and protease secretion.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari, piazza Giulio Cesare 11, 70124 Bari, Italy. avacca@hotmail.com
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Francesca
authors.initials: F
authors.lastname: Merchionne
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002352:Carrier Proteins / Q000032:analysis; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D039661:Integrin beta3 / Q000032:analysis; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis; D009101:Multiple Myeloma / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D019030:Receptors, Vitronectin / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; C409587:GRAP2 protein, human; D039661:Integrin beta3; D009363:Neoplasm Proteins; D019030:Receptors, Vitronectin; D019096:Vitronectin; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9