Osteopontin Expression in Gestational Trophoblastic Diseases: Correlation With Expression of the Adhesion Molecule, CEACAM1

Abstract

The human placenta is a complex tissue with multiple endocrine and nutritional functions and a unique capacity for rapid proliferation but tightly controlled invasion, differentiating it from malignant tumors. Osteopontin (OPN) is a glycoprotein of the extracellular matrix, which has been shown to mediate cellular migration and invasion and to contribute to tumorigenesis in several types of cancers. OPN also could be implicated in regulating implantation and placentation by promoting cellular migration and invasion in a placenta-specific fashion. We could demonstrate the expression pattern of OPN in the normal human placenta in which it is localized in the extravillous (intermediate) trophoblast and the villous cytotrophoblast. CEACAM1 is an adhesion molecule, which we have recently found to be expressed at the maternal-fetal interface of the normal placenta with a localization to the extravillous (invasive) trophoblast and in gestational trophoblastic disease (GTD) and also to be potentially implicated in trophoblast invasion and tumorigenesis. Both OPN and CEACAM1 have been shown to interact with integrin beta3. The purpose of this study was to investigate the expression pattern of OPN in GTD and to correlate it with the expression of CEACAM1. To analyze the expression of OPN, we performed immunohistochemistry on a total of 27 cases of GTD, including 21 hydatidiform moles and 6 choriocarcinomas, which had previously been characterized with respect to their CEACAM1 expression. Hydatidiform moles showed a positivity for OPN in villous cytotrophoblast and in the trophoblast proliferations on the villous surface. The strongest OPN expression could be observed in the choriocarcinomas with a heterogenous OPN expression pattern. CEACAM1 had shown similar results and was found to be expressed in choriocarcinoma. The expression pattern of osteopontin in gestational trophoblastic diseases indicates that it might play a role in the pathogenesis of GTD (possibly as a functional complex with CEACAM1 and integrin beta3) and might be useful as an additional diagnostic marker for such lesions.

CX3CL1 and CCL14 Regulate Extracellular Matrix and Adhesion Molecules in the Trophoblast: Potential Roles in Human Embryo Implantation1

“…Regulation of SPP1 at the maternal-fetal interface is proposed as important in mediating trophoblast adhesion and paracrine signaling events during implantation [33]. Importantly in conditions where uncontrolled trophoblast invasion occurs, such as gestational trophoblastic disease, SPP1 levels are increased, particularly in trophoblasts at the invasion front [36], highlighting the need for tight regulation of trophoblast invasion during implantation. CX3CL1 may contribute to the equilibrium of this highly invasive process, ensuring that trophoblast invasion is tightly restrained.…”

Osteopontin stimulates invasion of NCI‐h295 cells but is not associated with survival in adrenocortical carcinoma

“…Paracrine effects may provide protection from cytotoxic macrophages, possibly through inhibition of nitric acid production 26. Reported receptors for OPN are CD44, CEACAM1 27, 28, and a variety of integrins 29. Binding to integrin αvβ3 heterodimers via its RGD sequence has generally been accepted to be the primary receptor for OPN 30, 31.…”

Stimulation of CEACAM1 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and Calcium Ionophore A23187 in endometrial carcinoma cells and placental hybridoma cells

“…In contrast, increased CEA-CAM1 expression has been reported for carcinomas of the lung and stomach (26,27). We have also recently shown that CEACAM1 can act to enhance invasiveness in both melanoma (28) and trophoblast tumors (29).…”