RNA Aptamer Blockade of Osteopontin Inhibits Growth and Metastasis of MDA-MB231 Breast Cancer Cells

• DOI: 10.1038/mt.2008.235
• Publication Date: 2008-11-04T10:03:52Z
• Authors: Zhiyong Mi; Hongtao Guo; M Benjamin Russell; Yingmiao Liu; Bruce A Sullenger; Paul C Kuo
• Keywords: Osteopontin; MMP2

Osteopontin (OPN) is a secreted phosphoprotein which mediates tumorigenesis, local growth, and metastasis in variety of cancers. It potential therapeutic target for the regulation cancer metastasis. RNA aptamer technology targeting OPN may represent clinically viable therapy. In this study, we characterize critical sequence an aptamer, termed OPN-R3, directed against human OPN. has Kd 18 nmol/l binds specifically to as determined by electrophoretic mobility assays. MDA-MB231 breast cells examined under fluorescence microscopy, OPN-R3 ablates cell surface binding its CD44 αvβ3 integrin receptors. Critical enzymatic components signal transduction pathways, PI3K, JNK1/2, Src Akt, mediators extracellular matrix degradation, metalloproteinase 2 (MMP2) uroplasminogen activator (uPA), are significantly decreased following exposure OPN-R3. inhibits vitro adhesion, migration, invasion characteristics 60, 50, 65%, respectively. vivo xenograft model cancer, decreases progression distant metastases. On basis “proof-of-concept” conclude that biologically relevance modifying tumor growth