Recombinant entactin promotes mouse primary trophoblast cell adhesion and migration through the Arg-Gly-Asp (RGD) recognition sequence [published erratum appears in J Cell Biol 1993 Jul;122(1):279]

Abstract

Abstract. In vitro culture of mouse blastocysts during the period coinciding with implantation has revealed that primary trophoblast cells can adhere and migrate in serum-free medium when provided with certain extracellular matrix components, including fibronectin and laminin. Tightly associated with laminin is the glycoprotein, entactin, that may play an important role in basement membrane assembly and cell attachment. Mouse blastocysts were studied using this in vitro model to determine whether entactin was capable of mediating trophoblast invasive activity. Although entactin has never been shown to promote cell migration, we report here that recombinant entactin supported blastocyst outgrowth in a dose-dependent manner, with a maximal effect at 20-50/zg/ml. The ability of trophoblast cells to adhere and migrate on entactin was specifically inhibited by anti-entactin antibody, but not by antibodies raised against laminin. The synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, that contains the Arg-Gly-Asp (RGD) integrin recognition site, reversibly inhibited entactin-mediated blastocyst outgrowth in a dose-dependent manner, but had no effect on laminin-mediated outgrowth. The synthetic peptide, Gly-Phe-Arg-Gly-Asp-Gly-Gln, that comprises the actual RGD-containing sequence within entactin, promoted trophoblast outgrowth when immobilized on the substratum. Furthermore, a mutated recombinant entactin, altered to contain a Gin in place of Asp at the RGD site, provided no trophoblast cell adhesive activity. We conclude that entactin promotes trophoblast outgrowth through a mechanism mediated by the RGD recognition site, and that it may play an important role during invasion of the endometrial basement membrane at implantation.

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

“…A minor inhibition of NKp30-induced IL-2 production could be detected only at the highest rNID1 concentration. Since NID1 has been reported to interact with α3β1 (CD49a/CD29) and αvβ3 (CD51/CD61) integrins, 53,54 we analyzed the expression of CD29, CD49a, and CD61 in Bw-NKp44 and Bw-NKp30 cells, to rule out possible biases in the functional data on NID1. As shown in Fig.…”

“…In this context, it has been reported that NID1 may associate through the interaction of its RGD sequence with α3β1 or αvβ3 integrins. 53,54 Notably, we could detect surface NID1 on a panel of different NKp44Fc-binding human tumor cell lines (Figure 11). Although it has been reported that NID1 up-regulation occurs in several tumor types, information is still lacking on whether NID1 is associated to the tumor cell surface.…”

Uterine receptivity and embryo–uterine interactions in embryo implantation: lessons from mice

“…However, OPN null females do not show any reproductive defects and, therefore, other integrin activators must induce blastocyst activation corporately with OPN. In fact, both fibronectin and entactin, RGD motif-containing proteins, promote mouse blastocyst adhesion [26,27]. Although OPN is recently reported to be one of mediators in embryo-uterine interactions, HB-EGF is the one which was initially identified and is the most wellknown [1], and is fully described in the section ''Heparinbinding epidermal growth factor-like growth factor''.…”

Molecular and cellular events involved in the completion of blastocyst implantation

“…The invasive trophoblasts of mouse blastocysts adhere, spread, and migrate on extracellular matrix (ECM) substrates [36][37][38][39] and penetrate the three-dimensional ECM structures [40]. The TE of the implantation-induced blastocyst alters its functional programming via changes in cell surface molecules.…”