Breast cancer growth inhibition by delivery of the MDGI-derived peptide P108

Mammary derived growth inhibitor (MDGI) is a member of the family of cytopl asmic fatty acid binding proteins (FABPs), which bind hydrophobic ligands s uch as fatty acids, retinoids, eicosanoids and prostaglandines. MDGI and an 11 amino acid MDGI-derived conserved C-terminal peptide (P108) inhibits gr owth of normal mammary epithelial cells in tissue and organ culture, but fa ils to inhibit proliferation of many breast cancer cell Lines in vitro, Her e, the effects of peptide P108 on tumor growth of MCF-7, MDA-MB468 and MDA- MB231 human breast cancer cell lines in nude mice were tested. To deliver P 108 into tumors, a novel peptide production system was applied for expressi on and secretion of small bioactive peptides in mammalian cells. Functional differentiation was observed in MCF-7 and MDA-MB468 cells upon P108 expres sion, In addition, EGF-dependent colony formation in soft agar by MDA-MB468 cells was inhibited by secreted P108, Tumor growth in athymic nude mice wa s suppressed in all three cell lines tested, Furthermore, P108 expressed by MCF-7/P108 cells caused paracrine tumor growth inhibition of MDA-MB231 cel ls. These results indicate that breast cancer inhibition by P108 is indepen dent of binding to hydrophobic ligands and is perhaps mediated by interfere nce with EGF-dependent signaling pathways.