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Relationships of Prostaglandin E and Natural Killer Sensitivity to Metastatic Potential in Murine Mammary Adenocarcinomas¹

Department of Immunology, Michigan Cancer Foundation, Detroit, Michigan 48201

The levels of two prostaglandins (prostaglandins E and F) have been determined in a series of murine mammary lesions ranging from preneoplastic, hyperplastic alveolar nodules to highly metastatic adenocarcinomas. A highly positive correlation was seen between high levels of prostaglandin E and high tumorigenicity and metastatic potential. In addition, spontaneous metastasis of two highly metastatic tumors was partially inhibited by p.o. administration of indomethacin from the time of s.c. tumor transplantation until removal of the primary tumor at a limited size. Further, mammary tumor cells of differing metastatic potential were susceptible to polyinosinic-polycytidylic acid activated spleen lymphocytes in vitro. Cells of metastatic tumor lines (410.4 and 66) were more resistant to killing than were cells of two nonmetastatic tumor lines (168 and 410). The sensitivity of all target cells was increased when endogenous prostaglandin synthesis was prevented by the addition of indomethacin (1 µM) but was not affected by the lipoxygenase inhibitor nordihydroguaiaretic acid.

¹ Supported by Concern Foundation, The E. Walter Albachten Bequest, The United Foundation of Metropolitan Detroit, NIH Grant 27437, and NIH Grant 37943. A preliminary report was presented previously (1, 2).

² To whom requests for reprints should be addressed.

Received 12/11/84. Revised 6/13/85. Accepted 6/19/85.

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