Prostaglandin E 2 suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats

Ilan Yakar, Rivka Melamed, Guy Shakhar, Keren Shakhar, Ella Rosenne, Naphtali Abudarham, Gayle G. Page, Shamgar Ben-Eliyahu

Research output: Contribution to journalArticle

Abstract

Background: Prostaglandins (PGs) were shown in vitro to suppress several functions of cellular immunity. It is unclear, however, whether physiological levels of PGs can suppress cellular immunity in vivo and whether such suppression would compromise postoperative host resistance to metastasis. Methods: Fischer 344 rats were administered PGE 2 in doses (18 to 300 μg/kg subcutaneously) that increased the serum levels approximately 2- to 4-fold. We then assessed the number and activity of circulating natural killer (NK) cells, as well as rats' resistance to experimental metastasis of a syngeneic NK-sensitive tumor (MADB106). To study whether endogenously released PGs after surgery compromise these indices, we tested whether laparotomy adversely affects them and whether a cyclooxygenase-synthesis inhibitor, indomethacin (4 mg/kg), attenuates these effects. Results: PGE 2 dose-dependently suppressed NK activity per NK cell and dose-dependently increased 4- and 24-hour MADB106 lung tumor retention (LTR); 240 μg/kg of PGE 2 quadrupled the number of lung metastases counted 3 weeks later. Selective depletion of NK cells abrogated the promotion of LTR by PGE 2. Surgery significantly suppressed NK activity and increased MADB106 LTR, and indomethacin halved these effects without affecting nonoperated rats. Conclusions: PGE 2 is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence.

Original languageEnglish (US)
Pages (from-to)469-479
Number of pages11
JournalAnnals of surgical oncology
Volume10
Issue number4
DOIs
StatePublished - Dec 1 2003

Keywords

  • Animals
  • Cytotoxicity
  • NK cells
  • Tumor immunology

ASJC Scopus subject areas

  • Surgery
  • Oncology

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    Yakar, I., Melamed, R., Shakhar, G., Shakhar, K., Rosenne, E., Abudarham, N., Page, G. G., & Ben-Eliyahu, S. (2003). Prostaglandin E 2 suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats. Annals of surgical oncology, 10(4), 469-479. https://doi.org/10.1245/ASO.2003.08.017