Inhibition of breast cancer cell adhesion and bone metastasis by the extracellular adherence protein of Staphylococcus aureus

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Darius Schneider - , University Hospital Heidelberg (Author)
  • Lucy Liaw - (Author)
  • Carolin Daniel - (Author)
  • Athanasios N Athanasopoulos - (Author)
  • Mathias Herrmann - , Saarland University (Author)
  • Klaus T Preissner - (Author)
  • Peter P Nawroth - , Heidelberg University  (Author)
  • Triantafyllos Chavakis - , National Cancer Institute (NCI), Heidelberg University  (Author)

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.

Details

Original languageEnglish
Pages (from-to)282-288
Number of pages7
JournalBiochemical and biophysical research communications
Volume357
Issue number1
Publication statusPublished - 25 May 2007
Peer-reviewedYes
Externally publishedYes

External IDs

PubMedCentral PMC1913187
Scopus 34247118649

Keywords

Keywords

  • Bacterial Proteins/administration & dosage, Bone Neoplasms/pathology, Breast Neoplasms/pathology, Carcinoma/pathology, Cell Adhesion/drug effects, Cell Line, Tumor, Dose-Response Relationship, Drug, Humans, RNA-Binding Proteins/administration & dosage

Library keywords