Osteopontin Regulates Epithelial Mesenchymal Transition-Associated Growth of Hepatocellular Cancer in a Mouse Xenograft Model

摘要: OBJECTIVE To determine the efficacy of osteopontin (OPN) targeting in hepatocellular cancer (HCC). SUMMARY/BACKGROUND: OPN is associated with HCC growth and metastasis represents a unique therapeutic target. METHODS epithelial-mesenchymal transition (EMT) markers, α-smooth muscle actin (SMA), vimentin, tenascin-c, were measured archived human tissues from metastatic (n = 4) nonmetastatic settings. Additional studies utilized Sk-Hep-1 (high expression) Hep3b (low cells. An RNA aptamer (APT) that avidly binds (Kd 18 nM; t1/2 7 hours) ablates binding was developed. Adhesion, migration/invasion, EMT markers determined APT or mutant control (Mu-APT). RFP-Luc-Sk-Hep-1 implanted into NOD-scid mice livers followed by using bioluminescence imaging. After verification tumor growth, at week 3, (0.5 mg/kg; n Mu-APT injected q48h. When killed 8, cells reisolated assayed for markers. RESULTS significantly increased cohort. inhibited adhesion migration/invasion 5- 4-fold, respectively. decreased protein SMA, tenascin-c. In contrast, did not alter Hep3B adhesion, migration/invasion. slightly decreased. vivo model, weeks 6 to more than 10-fold. tenascin-c mRNAs 60%, 40%, 49%, respectively, RFP-positive recovered fluorescence-activated cell sorting (P < 0.04 vs all). CONCLUSIONS decreases HCC.