CNTO 95, a fully human anti alphav integrin antibody, inhibits cell signaling, migration, invasion, and spontaneous metastasis of human breast cancer cells.
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.
Chen
Qiming
Q
Oncology Research, Centocor R&D, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. qchen2@cntus.jnj.com
Manning
Carol D
CD
Millar
Hillary
H
McCabe
Francis L
FL
Ferrante
Catherine
C
Sharp
Celia
C
Shahied-Arruda
Lillian
L
Doshi
Parul
P
Nakada
Marian T
MT
Anderson
G Mark
GM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D019096:Vitronectin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D039564:Integrin alphaV; D051419:Paxillin; D019096:Vitronectin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C486839:intetumumab