Gesteigerte Expression pro-angiogenetischer Faktoren während Leberatrophie nach Pfortaderastligatur der Ratte — potentielle Bedeutung für malignes Wachstum

Abstract

Preoperative portal vein branch occlusion by either embolization or ligation has become a common strategy to prevent liver failure after prospectively planned extended hepatic resection in case of liver malignancies. The present study tests the hypothesis that portal deprivation induces cellular and molecular events which simultaneously promote tumor invasion and neo-angio-genesis, while regulating host tissue atrophy. To examine molecular responses during liver atrophy after portal occlusion, the rat model of 70% portal branch ligation (PAL) as a homologue was used. Northern blots were carried out to measure the mRNA expression of well defined invasion and neo-angiogenesis-related factors. The protein expression of the cellular VEGF-Receptors (flt-1 and flk-1) was examined by immunohisto chemistry. After a PAL, the portal-deprived tissue underwent shrinkage to 25% of its original mass by the massive occurrence of necrosis and apoptosis. VEGF- and PAI-1-specific mRNA was significantly elevated after PAL in the ligated lobes, and immunohistochemistry showed striking inductions of flt-1and flk-1 reactivity in hepatocytes and sinusoid linings 48 to 192 hours after PAL in the portal-deprived liver tissue. Given published evidence that PAI-1 is an important extracellular player in tumor invasion and VEGF and its recep-tors, flt-1and flk-1 are pivotal effectors of neo-angiogenesis, these results suggest that portal occlusive techniques promote tumor growth and invasion in the portal-deprived, atrophying liver tissue. These potential, unbeneficial cellular responses in tumor surrounding host liver tissue have to be reflected in the application of preoperative portal occlusive techniques.