CLONING OF A NOVEL MALIGNANT MELANOMA-DERIVED GROWTH-REGULATORY PROTEIN, MIA

Growth and progression of malignant melanoma cells is influenced by a complex network of growth-stimulating and -inhibiting factors produced by both the tumor cells and the local environment. Here we report the purification and molecular cloning of a novel growth regulating prote in, designated melanoma inhibitory activity (MIA) and provide a prelim inary functional characterization. MIA is translated as a 131-amino ac id precursor and processed into a mature 107-amino acid protein after cleavage of a putative secretion signal. A murine complementary DNA wa s isolated that encoded a MIA-protein with 88% amino acid identity. MI A is secreted into the culture supernatant by several malignant melano ma cell lines as an M(r) 11,000 autocrine growth factor and acts as a potent tumor cell growth inhibitor for malignant melanoma cells and so me other neuroectodermal tumors, including gliomas. MIA has no homolog y to any other known protein and, therefore, represents a novel type o f growth-regulatory factor. Furthermore, we describe a molecular appro ach to express functionally active MIA in Escherichia coli, which migh t be attractive as a future antitumor therapeutical substance.