Plasminogen fragment K1-3 inhibits expression of adhesion molecules and experimental HCC recurrence in the liver.
OBJECTIVE
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.


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.
Raskopf
Esther
E
Department of Internal Medicine I, University of Bonn, Bonn, Germany. Esther.Raskopf@ukb.uni-bonn.de
Gerceker
Sevil
S
Vogt
Annabelle
A
Standop
Jens
J
Sauerbruch
Tilman
T
Schmitz
Volker
V
D000256:Adenoviridae / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D018082:Kringles; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000494:pharmacology*; D010958:Plasminogen / Q000494:pharmacology*; D012008:Recurrence; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D015815:Cell Adhesion Molecules; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010958:Plasminogen; D020780:Matrix Metalloproteinase 9