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Minimal Antiproliferative Effect of Recombinant Mullerian Inhibiting Substance on Gynecological Tumor Cell Lines and Tumor Explants

Department of Cancer Research, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania [J. W. W., D. M. K., M. W. R., D. M., A. O.]; Biogen Corporation, Cambridge, Massachusetts [R. L. C., B. P.]; AntiCancer Inc. San Diego, California [R. M. H.] Pediatric Research Laboratory at the Massachusetts General Hospital, Boston, Massachusetts [P. K. D.]; and Department of Medicine, University of Texas Health Sciences Center, San Antonio, Texas [D. D. V. H.]

Mullerian Inhibiting Substance (MIS) is a testicular hormone that promotes involution of the Mullerian duct during embryogenesis. The Mullerian duct gives rise to adult female reproductive ducts including the fallopian tubes, uterus, and upper vagina. Thus, testicular MIS ensures the regression of female sex organ primordia. Partially purified bovine MIS was reported to inhibit proliferation of tumor cells derived from human gynecological cancers. These observations suggest that MIS might be an effective anticancer agent for some human tumors. Recombinant human MIS (rHu-MIS) has recently become available. To assess the antiproliferative activity of rHu-MIS, we examined its effects on 11 ovarian, six endometrial, and two nongynecological human tumor cell lines. rHu-MIS had no effect on proliferation of these cell lines in five independent assays. Forty-three primary human tumor explants were also examined in human tumor colony forming assays, gel-supported primary culture assays, and subrenal capsule assays. rHu-MIS significantly inhibited the growth of five of these tumors including four ovarian and one small cell lung cancer explant. The four ovarian cancer responses include three of 13 (23%) explants tested in human tumor colony-forming assays and one of eight (12.5%) explants tested in gel-supported primary culture assays. We conclude that rHu-MIS may have antiproliferative activity against some human ovarian cancers.

¹ To whom requests for reprints should be addressed, at Director—Cancer Research, MSDRL, Building 16-101, West Point, PA 19486.

Received 10/18/88. Revised 12/22/88. Accepted 1/16/89.

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