Tumor growth-promoting cellular host response during liver atrophy after portal occlusion.
OBJECTIVE
Clinical observations suggest cancer progression after preoperative segmental portal vein occlusion, a procedure to prevent liver failure after major hepatic resections. The aim of this study was to determine whether portal occlusion induces host reactions which promote cancer invasion and angiogenesis.


METHODS
The rat model of portal branch ligation (PBL) was compared with partial hepatectomy (PH) and sham operation (SO) and evaluated for the expression of heat shock protein-70 (hsp70), heme oxygenase-1 (hmox1), early growth response gene-1 (Egr-1) and urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1) and receptor (uPAR).


RESULTS
Portal deprivation after PBL was associated with a regression of liver tissue to 25% of its original mass within 8 days with only modest fibrotic changes. During the progression of atrophy, there were significant inductions of hsp70-, hmox1- and Egr-1-mRNA in comparison with regenerating liver tissue. PAI-1-specific mRNA was transiently elevated at 3 - 48 h after PBL in the atrophying lobes, whereas uPA and uPAR were unaffected in comparison with PH or SO.


CONCLUSIONS
Hepatic atrophy caused by PBL is associated with increased expression of genes known to promote tumor growth. These host events represent a possible explanation for the tumor progression after portal occlusion and require further evaluation.
Mueller
Lars
L
Department of Hepatobiliary Surgery and Visceral Transplantation, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. l.mueller@uke.uni-hamburg.de
Goettsche
Juliane
J
Abdulgawad
Awad
A
Vashist
Yogesh K
YK
Meyer
Jannine
J
Wilms
Christian
C
Hillert
Christian
C
Rogiers
Xavier
X
Broering
Dieter C
DC
D000818:Animals; D001284:Atrophy; D051766:Early Growth Response Protein 1 / Q000235:genetics; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006498:Hepatectomy / Q000009:adverse effects*; D008026:Ligation; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011169:Portal Vein; D011183:Postoperative Complications / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018840:HSP70 Heat-Shock Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D051547:Heme Oxygenase-1