CNTO 95 is a fully human
monoclonal antibody that recognizes alphav
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
alphav 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.