Abstract
Gestational choriocarcinoma (CC) is an aggressive cancer that develops upon the occurrence of abnormal pregnancies such as Hydatidiform moles (HMs) or upon non-molar pregnancies. CC cells often metastasize in multiple organs and can cause maternal death. Recent studies have established an association between recurrent HMs and mutations in the Nlrp7 gene. NLRP7 is a member of a new family of proteins that contributes to innate immune processes. Depending on its level of expression, NLRP7 can function in an inflammasome-dependent or independent pathway. To date, the role of NLRP7 in normal and in malignant human placentation remains to be elucidated. We have recently demonstrated that NLRP7 is overexpressed in CC trophoblast cells and may contribute to their acquisition of immune tolerance via the regulation of key immune tolerance-associated factors, namely HLA family, βCG and PD-L1. We have also demonstrated that NLRP7 increases trophoblast proliferation and decreases their differentiation, both in normal and tumor conditions. Actual findings suggest that NLRP7 expression may ensure a strong tolerance of the trophoblast by the maternal immune system during normal pregnancy and may directly affect the behavior and aggressiveness of malignant trophoblast cells. The proposed review summarizes recent advances in the understanding of the significance of NLRP7 overexpression in CC and discusses its multifaceted roles, including its function in an inflammasome-dependent or independent pathways.
Highlights
The placenta is a highly specialized organ that develops during pregnancy to ensure the growth and the normal progress of the pregnancy
In relation to pregnancy pathologies, we demonstrated that NLRP7 expression is elevated in the placentae of pregnancies complicated by fetal growth restriction (FGR), a pregnancy often characterized by increased inflammation [13,20,52,53]
We used three approaches to define the role of NLRP7: (i) a clinical study in which we used human sera and placentae that were collected from normal pregnant women and from patients with complete hydatidiform moles (CHM) or CC; (ii) an in vitro study in which we investigated the influence of NLRP7 knockdown on the tumorigenesis of the choriocarcinoma cell line, JEG3, which used both
Summary
The placenta is a highly specialized organ that develops during pregnancy to ensure the growth and the normal progress of the pregnancy. Migratory and invasive characteristics of EVT, the initial low capacitance/high resistance of the uterine arteries is converted into high capacitance/low resistance vessels Upon this invasion, the fetomaternal circulation is established, allowing for an increase in oxygen pressure within the intervillous space, from 20 mmHg in the early first trimester to 55 mmHg in the late first trimester of pregnancy [7]. Failure in the process of invasion of trophoblast cells into the maternal decidua has been reported to cause deregulations in the production of multiple factors, including inflammatory cytokines, reactive oxygen species (ROS) and other harmful molecules, such as uric acid [8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
