Recombinant Human Mullerian Inhibiting Substance Inhibits Human Ocular Melanoma Cell Lines in Vitro and in Vivo1

Since Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian duct, the anlagen of the uterus, vagina, and fallopian tube, we expected and have previously observed that purified recombinant human MIS causes regression of gynecological tumors. However, recent exper iments indicating that neural crest derivatives might be responsive to MIS prompted study of a group of human ocular melanoma cell lines in 4 in vitro inhibition assays, and a subrenal capsule assay in vivo. Ocular melanoma cell lines that grew well in a respective assay were studied with MIS to determine whether this biological modifier could inhibit growth. Three human ocular melanomas, OM431 (/" < 0.01), OM467 (/' < 0.02), and OM482 (/' < 0.03), were growth-inhibited by highly purified human recombinant MIS in soft agarose. A dose-dependent tumor inhibition was noted when OM431 cells were incubated with MIS in a liquid colony inhibition assay (f < 0.05). In addition, OM467 was inhibited ( /' < 0.05) by MIS in a multicellular tumor spheroid assay. Cell cycle analysis indicated that OM431 cells were inhibited in monolayer by MIS while in d. At 100-fold lower serum concentrations than required in the media of in vitro assays, MIS delivered via i.p. osmotic pumps inhibited (P < 0.05) in vivo the growth of OM431 implanted beneath the renal capsule of nude and CD-I irradiated mice when compared to mice given implants of pumps containing no MIS. The responsiveness of ocular melanoma to MIS broadens the spectrum of tumors that might be treated with MIS and suggests further investigation of other neural crest tumors.