Clinical & Experimental Metastasis

, Volume 25, Issue 2, pp 139–148 | Cite as

CNTO 95, a fully human anti αv integrin antibody, inhibits cell signaling, migration, invasion, and spontaneous metastasis of human breast cancer cells

  • Qiming Chen
  • Carol D. Manning
  • Hillary Millar
  • Francis L. McCabe
  • Catherine Ferrante
  • Celia Sharp
  • Lillian Shahied-Arruda
  • Parul Doshi
  • Marian T. Nakada
  • G. Mark Anderson
Research Paper

Abstract

CNTO 95 is a fully human monoclonal antibody that recognizes αv integrins. Previous studies have shown that CNTO 95 exhibits both anti-tumor and anti-angiogenic activities (Trikha M et al., Int J Cancer 110:326–335, 2004). In this study we investigated the biological activities of CNTO 95 on breast tumor cells both in vitro and in vivo. In vitro treatment with CNTO 95 decreased the viability of breast tumor cells adhering to vitronectin. CNTO 95 inhibited tumor cell adhesion, migration, and invasion in vitro. CNTO 95 treatment also induced tyrosine dephosphorylation of focal adhesion kinase (FAK), and the docking protein paxillin that recruits both structural and signaling molecules to focal adhesions (Turner CE, Int J Biochem Cell Biol 30:955–959, 1998; O’Neil GM et al., Trends Cell Biol 10:111–119, 2000). These results suggest that CNTO 95 inhibits breast tumor cell growth, migration and invasion by interruption of αv integrin mediated focal adhesions and cell motility signals. In vivo studies of CNTO 95 were conducted in an orthotopic breast tumor xenograft model. Treatment with CNTO 95 resulted in significant inhibition of both tumor growth and spontaneous metastasis of MDA-MB-231 cells to the lungs. CNTO 95 also inhibited lung metastasis in a separate experimental (tail vein injection) model of metastasis. The results presented here demonstrate the anti-tumor and anti-metastatic activities of CNTO 95 in breast cancer models and provide insight into the cellular and molecular mechanisms mediating its inhibitory effects on metastasis.

Keywords

CNTO 95 αv integrin Cell migration Cell invasion MCF-7 MDA-MB-231 MDA-MB-468 MX-1 Breast cancer Focal adhesion kinase Paxillin Lung metastasis 

Notes

Acknowledgements

We thank Paul Marsters for his help in statistical analysis and Ray Heslip for his help preparing graphs.

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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Qiming Chen
    • 1
  • Carol D. Manning
    • 1
  • Hillary Millar
    • 1
  • Francis L. McCabe
    • 1
  • Catherine Ferrante
    • 1
  • Celia Sharp
    • 1
  • Lillian Shahied-Arruda
    • 1
  • Parul Doshi
    • 1
  • Marian T. Nakada
    • 1
  • G. Mark Anderson
    • 1
  1. 1.Oncology ResearchCentocor R&D, Inc.RadnorUSA

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