Melanoma-inhibiting activity inhibits cell proliferation by prolongation of the S-phase and arrest of cells in the G2 compartment.

Autocrine-secreted melanoma tumor growth-inhibiting activity (MIA, approximately Mr 8000) was isolated from supernatants of a malignant melanoma cell line HTZ-19 dM, established from a central nervous system-melanoma metastasis. Cell cycle kinetic analysis performed with bromodeoxyuridine/Hoechst flow cytometry revealed a MIA-sensitive period at the G0/G1 to S traverse; MIA mediated prolongation of the S-phase and increased arrest of cells in the G2 compartment. Growth inhibition by MIA is cell-density dependent; maximal effect is seen at low densities, and the effect may be partially antagonized by whole serum. MIA may cause growth stimulation at high cell densities and low MIA concentrations. The effect of MIA on different histological neuroectodermal cell types was compared by the same methodology: proliferation of a second malignant melanoma was inhibited, and no effect was observed with an ependymoma; 2 glioblastomas were slightly stimulated. Effects on human fibroblast-like cell strains were inconsistent. The mechanism of MIA is discussed in relation to other endogenous autocrine growth inhibitors.