Multiple facets of sialomucin complex/MUC4, a membrane mucin and ErbB2 ligand, in tumors and tissues (Y2K update)

Sialomucin complex (SMC, MUC4) is a high Mr glycoprotein heterodimer, compo sed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. ASGP-2 contains two EGF-like domains and acts as an intramembrane ligand for the receptor t yrosine kinase ErbB2. Transfection studies with SMC DNAs showed that SMC ex pression could markedly reduce both cell-cell and cell-matrix interactions in vitro and increase the growth of primary tumors and the formation of met astatic foci of human A375 melanoma cells as xenotransplants in nude mice, possibly through the ability to suppress apoptosis. SMC is expressed in mos t vulnerable epithelia as a protective agent, which is found in both membra ne and soluble forms at luminal surfaces and secreted into fluids such as m ilk and tears. SMC appears to be constitutively expressed by most accessibl e epithelia, notable exceptions being the mammary gland and uterine luminal epithelium, in which it is tightly regulated during pregnancy. Down-regula tion at the luminal uterine surface appears necessary for blastocyst implan tation. TGF-b is a potent repressor of SMC expression in the mammary gland and uterus, though by different mechanisms. These combined results suggest that SMC has multiple functions in epithelia and is tightly regulated in th ose tissues where its special functions are required.