Preoperative dietary restriction reduces hepatic tumor load by reduced E-selectin-mediated adhesion in mice.
BACKGROUND
Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery-induced inflammation and subsequent adhesion of circulating tumor cells.


METHODS
BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra-splenic injection of 5.0 x 10(4) C26-colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed.


RESULTS
Preoperative dietary restriction significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043).


CONCLUSIONS
Preoperative dietary restriction reduces hepatic tumor load after injection with tumor cells. Reduced adhesion to endothelial cells and reduced mRNA expression of E-selectin suggest that dietary restriction reduces tumor load by lowering the adhesion of circulating tumor cells to hepatic vascular endothelium.
van Ginhoven
Tessa M
TM
Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
van den Berg
Jan Willem
JW
Dik
Willem A
WA
Ijzermans
Jan N M
JN
de Bruin
Ron W F
RW
D000818:Animals; D031204:Caloric Restriction; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D019040:E-Selectin / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009360:Neoplastic Cells, Circulating; D016133:Polymerase Chain Reaction; D047368:Tumor Burden
D019040:E-Selectin