PURPOSE: There is no established adjuvant or neo-adjuvant treatment to curb tumor recurrence of hepatocellular carcinoma (HCC). Recent data showed that angiostatic factors can inhibit tumor cell adhesion to the endothelium and therefore recurrence/metastasis. We tested a potential preventive, pre-operative strategy using plasminogen kringles 1-3 (K1-3) to overcome this hurdle. MATERIALS AND METHODS: Effects of K1-3 on the intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) expression was analyzed in vitro and in vivo on RNA and protein levels. Influence of K1-3 on HCC recurrence in the liver was analyzed in an orthotopic tumor model. RESULTS: K1-3 decreased ICAM expression in Hepa129 tumor cells and VCAM expression in SVEC4-10 endothelial cells in vitro. In vivo, ICAM was reduced in histological tumor sections. Preventive treatment with AdK1-3 inhibited experimental HCC recurrence and tumor growth in the liver. CONCLUSIONS: We were able to show that K1-3 inhibits intrahepatic tumor recurrence. This novel aspect elucidates a possible approach to prevent HCC recurrence.
PURPOSE: There is no established adjuvant or neo-adjuvant treatment to curb tumor recurrence of hepatocellular carcinoma (HCC). Recent data showed that angiostatic factors can inhibit tumor cell adhesion to the endothelium and therefore recurrence/metastasis. We tested a potential preventive, pre-operative strategy using plasminogen kringles 1-3 (K1-3) to overcome this hurdle. MATERIALS AND METHODS: Effects of K1-3 on the intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) expression was analyzed in vitro and in vivo on RNA and protein levels. Influence of K1-3 on HCC recurrence in the liver was analyzed in an orthotopic tumor model. RESULTS:K1-3 decreased ICAM expression in Hepa129 tumor cells and VCAM expression in SVEC4-10 endothelial cells in vitro. In vivo, ICAM was reduced in histological tumor sections. Preventive treatment with AdK1-3 inhibited experimental HCC recurrence and tumor growth in the liver. CONCLUSIONS: We were able to show that K1-3 inhibits intrahepatic tumor recurrence. This novel aspect elucidates a possible approach to prevent HCC recurrence.
Authors: Volker Schmitz; Esther Raskopf; Maria Angeles Gonzalez-Carmona; Annabelle Vogt; Christian Rabe; Ludger Leifeld; Miroslaw Kornek; Tilman Sauerbruch; Wolfgang H Caselmann Journal: Gut Date: 2006-06-29 Impact factor: 23.059
Authors: S Indraccolo; M Morini; E Gola; F Carrozzino; W Habeler; S Minghelli; L Santi; L Chieco-Bianchi; Y Cao; A Albini; D M Noonan Journal: Cancer Res Date: 2001-07-15 Impact factor: 12.701
Authors: L Mendoza; T Carrascal; M De Luca; A M Fuentes; C Salado; J Blanco; F Vidal-Vanaclocha Journal: Hepatology Date: 2001-08 Impact factor: 17.425
Authors: E Frau; C Magnon; P Opolon; E Connault; D Opolon; F Beermann; F Beerman; M Abitbol; M Perricaudet; C Bouquet Journal: Cancer Gene Ther Date: 2006-11-03 Impact factor: 5.987