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 experiments 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 (P less than 0.01), OM467 (P less than 0.02), and OM482 (P less than 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 (P less than 0.05). In addition, OM467 was inhibited (P less than 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 G1. At 100-fold lower serum concentrations than required in the media of in vitro assays, MIS delivered via i.p. osmotic pumps inhibited (P less than 0.05) in vivo the growth of OM431 implanted beneath the renal
capsule of nude and CD-1 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.