Mullerian Inhibiting Substance inhibits invasion and migration of epithelial cancer cell lines

ObjectiveGiven the fact that Mullerian Inhibiting Substance (MIS) causes complex remodeling of the urogenital ridge and regression of the Mullerian ducts during male embryonic development, we examined whether MIS could affect similar cell properties such as migration and invasion that could contribute ultimately to micro-metastasis of cancers arising from Mullerian tissues. MIS receptor expressing cell lines found to be invasive and migratory in vivo are examined in an in vivo assay that is cost-effective.MethodsWe designed in vitro and in vivo experiments to determine if MIS inhibited the movement of cancer lines IGROV-1, HEp3, MDA-MB-231, and HT1080 in cell culture invasion/migration chamber assays and in chick embryo metastasis assays.ResultsMIS, at concentrations below those that inhibit cell proliferation, blocked in vitro invasion and in vivo migration of epithelial cancer cells that express the MIS receptor.ConclusionsWhile our laboratory has previously established MIS as an inhibitor of cancer cell proliferation using in vitro assays and in vivo xenografts, we now show that MIS can also inhibit in vivo tumor migration.

Research Highlights
► Mullerian Inhibiting Substance (MIS) blocks inhibits cancer cell invasion in vitro.
► MIS blocks invasion and migration of cancer cell lines in vivo.
► Inhibition of cell migration by MIS is independent of its effect on cell division.
► Mullerian Inhibiting Substance may inhibit human ovarian cancer metastasic processes.