Annals of Surgical Oncology

, Volume 23, Supplement 2, pp 257–265 | Cite as

Abdominal Infection Suppresses the Number and Activity of Intrahepatic Natural Killer Cells and Promotes Tumor Growth in a Murine Liver Metastasis Model

  • Yusuke Matsumoto
  • Hironori Tsujimoto
  • Satoshi Ono
  • Nariyoshi Shinomiya
  • Hiromi Miyazaki
  • Shuichi Hiraki
  • Risa Takahata
  • Kazumichi Yoshida
  • Daizoh Saitoh
  • Takao Yamori
  • Junji Yamamoto
  • Kazuo Hase
Gastrointestinal Oncology

Abstract

Background

Increasing evidence suggests that postoperative infection is associated with poorer long-term outcome in various malignancies. However, the mechanism of poor prognosis induced by postoperative infection has not been clearly explained. We sought to determine whether abdominal infection promotes cancer metastases in a murine liver metastasis model, and to investigate the role of liver natural killer (NK) cells on antitumor immunity during abdominal infection.

Methods

Female BALB/c (8–10 weeks old) mice were inoculated with NL-17 colon cancer cells into the spleen and then subjected to abdominal infection induced by cecal ligation and puncture (CLP) or sham treatment. The extent of liver metastases and cytokine production in the serum and liver were investigated. Cell fraction and cytotoxic activities of liver mononuclear cells (MNCs) were elucidated.

Results

CLP mice had poorer survival and their serum levels of IL-6, -10, and -12p70 were significantly elevated on day 1 compared with sham-treated and control mice. No obvious differences in cytokine levels of the liver homogenates were identified among the three groups, except IL-12p70 levels in CLP mice on day 7 significantly decreased. The cytotoxic activities of liver MNCs were significantly suppressed in CLP mice soon after tumor inoculation. Flow cytometry revealed a decrease in NK cells in the liver and perforin and granzyme B expression levels.

Conclusions

Abdominal infection promoted liver metastases in a murine liver metastasis model, which may be partially caused by a decrease in the number and activity of NK cells during abdominal infection.

Keywords

Natural Killer Cell Liver Metastasis Cytotoxic Activity Liver Homogenate Roswell Park Memorial Institute 

Notes

Acknowledgment

The authors are grateful to Kouji Matsumura (Central Research Laboratory, National Defense Medical College, Saitama, Japan) for his technical support concerning cell culture.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10434_2015_4466_MOESM1_ESM.pdf (29 kb)
Analyses of cytokine levels in the liver homogenates in CLP and sham mice without tumor inoculation. There were no differences of cytokine levels in the liver homogenates in CLP and sham mice without tumor inoculation (n=4). Each experiment was independently performed 3 times with similar results. Representative data are depicted.White bar = sham mice, black bars = CLP mice (PDF 29 kb)

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Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Yusuke Matsumoto
    • 1
  • Hironori Tsujimoto
    • 1
  • Satoshi Ono
    • 2
  • Nariyoshi Shinomiya
    • 3
  • Hiromi Miyazaki
    • 2
  • Shuichi Hiraki
    • 1
  • Risa Takahata
    • 1
  • Kazumichi Yoshida
    • 1
  • Daizoh Saitoh
    • 2
  • Takao Yamori
    • 4
  • Junji Yamamoto
    • 1
  • Kazuo Hase
    • 1
  1. 1.Department of SurgeryNational Defense Medical CollegeTokorozawaJapan
  2. 2.Division of TraumatologyNational Defense Medical CollegeTokorozawaJapan
  3. 3.Department of Integrative Physiology and Bio-Nano MedicineNational Defense Medical CollegeTokorozawaJapan
  4. 4.Division of Molecular Pharmacology, Cancer Chemotherapy CenterJapanese Foundation for Cancer ResearchTokyoJapan

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