Induction of E-selectin after partial hepatectomy promotes metastases to liver in mice.
BACKGROUND
The liver is the most frequent site of tumor metastasis. It has been suggested that partial hepatectomy promotes liver metastasis of malignant disease and that expression of E-selectin, a cell adhesion molecule, plays roles in tumor metastasis. However, no reports are available concerning the expression of E-selectin after hepatectomy.


METHODS
In the present study, we used BALB/c mice subjected to 30% partial hepatectomy after injection of 1 x 10(4) colon 26 cells to determine the effects of partial hepatectomy on tumor metastasis to liver. E-Selectin expression within the liver after partial hepatectomy was evaluated using reverse transcription polymerase chain reaction and Western blotting. In addition, we injected polyclonal antibody to E-selectin into mice in which partial hepatectomy had augmented liver metastasis.


RESULTS
Mice subjected to partial hepatectomy had significantly increased numbers of liver metastases (sham operation, 1.5 +/- 2.0, vs partial hepatectomy, 35.5 +/- 19.3; P < 0.001). Expression of E-selectin mRNA within the liver was markedly increased 4 h after partial hepatectomy, but subsequently decreased at 24 h. E-Selectin protein was detected 8 h after hepatectomy, but subsequently decreased at 24 h as measured by Western blotting. Mice subjected to intraperitoneal injection of neutralizing antibody after operation had significantly decreased numbers of liver metastases (phosphate-buffered saline, 20.6 +/- 9.2, P < 0.05, and normal IgG, 18.0 +/- 8.0, P < 0.05, compared with polyclonal antibody to E-selectin, 5.6 +/- 4.8).


CONCLUSIONS
Induction of E-selectin by partial hepatectomy promotes hematogenous liver metastasis. Our findings can be applied to surgical treatment of liver tumor to reduce the recurrence of liver metastasis after hepatectomy by inhibiting E-selectin-mediated adhesion using reagents to E-selectin.
Second Department of Surgery, Faculty of Medicine, Toyama, 930-0194, Japan. uohide@toyama-mpu.ac.jp
H
H
Uotani
I
I
Yamashita
T
T
Nagata
H
H
Kishimoto
Y
Y
Kashii
K
K
Tsukada
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019040:E-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006498:Hepatectomy / Q000379:methods; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011169:Portal Vein; D011184:Postoperative Period; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019040:E-Selectin; D012333:RNA, Messenger