Role of NLRP7 in Normal and Malignant Trophoblast Cells

Biomedicines

Tiphaine Raia-Barjat¹  Christel Marquette²  Roland Abi Nahed²  Thierry Michy²  Maya Elkhoury Mikhael²  Constance Collet²  Nadia Alfaidy²  Nicolas Lemaitre²  Frederic Sergent²  Deborah Reynaud²  Pascale Hoffmann²  Mohamed Benharouga²  Padma Murthi³ 

[1] Department of Gynecology and Obstetrics, University Hospital, 42100 Saint Etienne, France;Institut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38054 Grenoble, France;Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3168, Australia;

关键词: NLRP7;    inflammasome;    choriocarcinoma;    pregnancy;    maternal immune tolerance;    tumor microenvironment;   

DOI  :  10.3390/biomedicines10020252

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown