Chen Qiming, Manning Carol D, Millar Hillary, McCabe Francis L, Ferrante Catherine, Sharp Celia, Shahied-Arruda Lillian, Doshi Parul, Nakada Marian T, Anderson G Mark
Oncology Research, Centocor R&D, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA.
Clin Exp Metastasis. 2008;25(2):139-48. doi: 10.1007/s10585-007-9132-4. Epub 2007 Dec 5.
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.
CNTO 95是一种可识别αv整合素的全人源单克隆抗体。先前的研究表明，CNTO 95具有抗肿瘤和抗血管生成活性（Trikha M等人，《国际癌症杂志》110:326 - 335，2004年）。在本研究中，我们在体外和体内研究了CNTO 95对乳腺肿瘤细胞的生物学活性。用CNTO 95进行体外处理可降低黏附于玻连蛋白的乳腺肿瘤细胞的活力。CNTO 95在体外抑制肿瘤细胞的黏附、迁移和侵袭。CNTO 95处理还诱导了黏着斑激酶（FAK）以及对接蛋白桩蛋白的酪氨酸去磷酸化，桩蛋白可将结构和信号分子募集到黏着斑（Turner CE，《国际生物化学与细胞生物学杂志》30:955 - 959，1998年；O'Neil GM等人，《细胞生物学趋势》10:111 - 119，2000年）。这些结果表明，CNTO 95通过中断αv整合素介导的黏着斑和细胞运动信号来抑制乳腺肿瘤细胞的生长、迁移和侵袭。在原位乳腺肿瘤异种移植模型中对CNTO 95进行了体内研究。用CNTO 95处理可显著抑制MDA - MB - 231细胞的肿瘤生长和向肺部的自发转移。在另一个单独的转移实验（尾静脉注射）模型中，CNTO 95也抑制了肺转移。此处呈现的结果证明了CNTO 95在乳腺癌模型中的抗肿瘤和抗转移活性，并深入了解了介导其对转移抑制作用的细胞和分子机制。
