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 that shares similarities with the invasive behavior of tumor cells. In the present investigation, a cDNA subtraction library was constructed between invasive trophoblast at day 8 of murine development and mature noninvasive placenta at day 18 of gestation. One of the differentially expressed clones, Epcs26, was mapped to the X chromosome and revealed no homology to any known gene. It was predominantly expressed in parietal endoderm, undifferentiated cells of the ectoplacental cone, and a few trophoblast giant cells. Another gene, designated Epcs50, was mapped to chromosome 19. It exhibited homologies to the mouse Mps1 gene and, like Mps1, may have a distant relationship to the lytic protein perforin. High expression was detected in parietal endoderm cells and in a subset of secondary trophoblast giant cells. Two sequences, Epcs24 and Epcs68, exhibited an extensive open reading frame that shared the common features of the cysteine proteinase cathepsin L. Expression was confined to an undefined subpopulation of trophoblast giant cells. Both genes were mapped to chromosome 13 in close proximity to cathepsins L and I. The known functions of MPS1 and cathepsin L proteins indicate that the related proteins EPCS50, EPCS24, and EPCS68 participate in conferring invasive properties to the mouse trophoblast. (C) 2000 Academic Press.