cDNA subtraction cloning reveals novel genes whose temporal and spatial expression indicates association with trophoblast invasion

Trophoblast invasion is a critical process in development of most mammals t hat shares similarities with the invasive behavior of tumor cells. In the p resent investigation, a cDNA subtraction library was constructed between in vasive trophoblast at day 8 of murine development and mature noninvasive pl acenta at day 18 of gestation. One of the differentially expressed clones, Epcs26, was mapped to the X chromosome and revealed no homology to any know n gene. It was predominantly expressed in parietal endoderm, undifferentiat ed cells of the ectoplacental cone, and a few trophoblast giant cells. Anot her gene, designated Epcs50, was mapped to chromosome 19. It exhibited homo logies to the mouse Mps1 gene and, like Mps1, may have a distant relationsh ip to the lytic protein perforin. High expression was detected in parietal endoderm cells and in a subset of secondary trophoblast giant cells. Two se quences, Epcs24 and Epcs68, exhibited an extensive open reading frame that shared the common features of the cysteine proteinase cathepsin L. Expressi on was confined to an undefined subpopulation of trophoblast giant cells. B oth genes were mapped to chromosome 13 in close proximity to cathepsins L a nd I. The known functions of MPS1 and cathepsin L proteins indicate that th e related proteins EPCS50, EPCS24, and EPCS68 participate in conferring inv asive properties to the mouse trophoblast. (C) 2000 Academic Press.