Human müllerian inhibiting substance inhibits tumor growth in vitro and in vivo

Abstract

Müllerian inhibiting substance (MIS) causes regression of the müllerian duct in the male fetus. Bovine MIS has been reported to inhibit the growth of some gynecological tumors. Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells has been highly purified by immunoaffinity chromatography. The introduction of a salt wash prior to elution of MIS from the affinity column removes a growth-stimulating factor(s) derived from Chinese hamster ovary cells. This immunopurified rhMIS caused significant inhibition (34-59% survival) of A431 (a vulvar epidermoid carcinoma), HT-3 (a cervical carcinoma), HEC-1-A (an endometrial adenocarcinoma), NIH:OVCAR-3 (an ovarian adenocarcinoma), and OM431 (an ocular melanoma) human cell lines in colony inhibition assays. Two cell lines, Hep 3B (a hepatocellular carcinoma) and RT4 (a bladder transitional cell papilloma), were unresponsive to immunopurified rhMIS. Using an in vivo subrenal capsule assay in irradiated CD-1 mice, the growth of A431 and OM431 cells was inhibited by immunopurified rhMIS. We conclude that rhMIS inhibits the growth of certain tumor cell lines in vitro and in vivo.