αvβ3 integrin engagement enhances cell invasiveness in human multiple myeloma

Roberto Ria, Angelo Vacca, Domenico Ribatti, Francesco Di Raimondo, Francesca Merchionne, Franco Dammacco

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. 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). Design and 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 antiαvβ3 integrin antibody. Integrin engagement caused aggregation of the plaques, which contained the β3 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 αvβ33 integrin-dependent manner. Interpretation and Conclusions. This ability of myeloma plasma cells to interact with VN and FN via αvβ3 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.

Original languageEnglish
Pages (from-to)836-845
Number of pages10
JournalHaematologica
Volume87
Issue number8
Publication statusPublished - 2002

Keywords

  • Extracellular matrix
  • Focal adhesion
  • Matrix metalloproteinases
  • Multiple myeloma
  • Urokinase-type plasminogen activator

ASJC Scopus subject areas

  • Hematology

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