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Prostaglandin E2 Suppresses NK Activity In Vivo and Promotes Postoperative Tumor Metastasis in Rats

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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 PGE2 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: PGE2 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 PGE2 quadrupled the number of lung metastases counted 3 weeks later. Selective depletion of NK cells abrogated the promotion of LTR by PGE2. Surgery significantly suppressed NK activity and increased MADB106 LTR, and indomethacin halved these effects without affecting nonoperated rats.

Conclusions:PGE2 is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence.

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Authors and Affiliations

  1. Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel

    Ilan Yakar MA, Rivka Melamed MSc, Guy Shakhar MSc, Keren Shakhar MA, Ella Rosenne MSc & Naphtali Abudarham MA

  2. School of Nursing, Johns Hopkins University, Baltimore, Maryland

    Gayle G. Page DNSc & Shamgar Ben-Eliyahu PhD

  3. Department of Psychology, Tel Aviv University, Tel Aviv 69978, Israel

    Shamgar Ben-Eliyahu PhD

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  1. Ilan Yakar MA
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  2. Rivka Melamed MSc
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  3. Guy Shakhar MSc
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Correspondence to Shamgar Ben-Eliyahu PhD.

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Yakar, I., Melamed, R., Shakhar, G. et al. Prostaglandin E2 Suppresses NK Activity In Vivo and Promotes Postoperative Tumor Metastasis in Rats. Ann Surg Oncol 10, 469–479 (2003). https://doi.org/10.1245/ASO.2003.08.017

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  • DOI: https://doi.org/10.1245/ASO.2003.08.017

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