title: Inhibition of breast cancer cell adhesion and bone metastasis by the extracellular adherence protein of Staphylococcus aureus.
abstract: Bone metastasis is a common sequelae of breast cancer and the interaction of alpha v beta3-integrin with osteopontin (OPN) found in the extracellular matrix of mineralized tissues is implicated in this process. The integrin-dependent proadhesive and promigratory functions of OPN are particularly attributed to the 40 kD N-terminal fragment that derives upon matrix metalloproteinase (MMP) cleavage. Based on the broad repertoire of interactions between Staphylococcus aureus extracellular adherence protein (Eap) and host components, we here characterized Eap to specifically interact with recombinant full-length OPN and the 40 kD N-terminal MMP cleavage fragment, but not with the 32 kD or the 25 kD C-terminal fragments of OPN. Eap thereby prevented the OPN/alpha v beta3-integrin interaction, as well as the alpha v beta3-integrin-dependent adhesion of MDA-MB-231 breast cancer cells to full-length OPN or to the 40 kD fragment and the migration of these cells towards OPN. Furthermore, Eap treatment markedly impaired the development of osseous metastasis of human MDA-MB-231 cells in vivo. Taken together, Eap may represent an attractive novel treatment for the prevention of breast cancer bone metastasis.
authors.affiliation: Department of Internal Medicine, University Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Schneider
authors.forename: Lucy
authors.initials: L
authors.lastname: Liaw
authors.forename: Carolin
authors.initials: C
authors.lastname: Daniel
authors.forename: Athanasios N
authors.initials: AN
authors.lastname: Athanasopoulos
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D001426:Bacterial Proteins / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002277:Carcinoma / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016601:RNA-Binding Proteins / Q000008:administration & dosage*
chemical_list: D001426:Bacterial Proteins; C444739:Eap-N protein, Staphylococcus aureus; D016601:RNA-Binding Proteins