COMPLEMENTARY EXPRESSION OF HIP, A CELL-SURFACE HEPARAN-SULFATE BINDING-PROTEIN, AND PERLECAN AT THE HUMAN FETAL-MATERNAL INTERFACE

The human hemochorial placenta is a structure formed by the invasion o f cytotrophoblasts into the uterus. Previous studies from our laborato ry have demonstrated a role for heparan sulfate proteoglycans (HSPGs) and their binding proteins in interactions between human trophoblastic and uterine cell lines in vitro. In this study, expression of both mR NA and protein of a novel, cell surface, heparin/heparan sulfate inter acting protein (HIP), by human trophoblastic cell lines-i.e., JAR, JEG , and BeWo-and by human cytotrophoblast was examined throughout gestat ion. Immunohistochemistry of the human fetal-maternal interface demons trated abundant HIP expression in cytotrophoblast cells, with lesser s taining in syncytiotrophoblast and little or no staining in surroundin g stromal or decidual cells. Staining with antibodies to the basement membrane HSPG, perlecan, demonstrated a pattern of staining complement ary to that of HIP. Cytotrophoblasts in the uterine stroma, not affili ated with attached villi, displayed a less intense deposition of perle can. In vitro binding studies of I-125-perlecan to 17-amino acid synth etic peptide sequence of HIP, which has a high affinity and specificit y for heparin/heparan sulfate, indicates that perlecan binds to the HI P peptide with high affinity (K-Dapp = 0.6 nM) and in a heparin-inhibi table manner. Furthermore, HIP antibodies inhibited by 61-88% in vitro invasion by trophoblasts in assays using primary cultures of normal h uman cytotrophoblasts. Consistent with this was the observation that i mmunohistochemically detectable HIP expression was greatly reduced in preeclamptic cytotrophoblasts, a condition in which trophoblast invasi on is abnormally shallow. It is suggested that HIP potentiates human c ytotrophoblast interactions with HSPGs, In vivo, and facilitates troph oblast invasion processes.