Choriocarcinoma is a veritable placental cancer that develops upon abnormal pregnancies named Hydatidiform Moles (HMs). Choriocarcinoma can metastasis in multiple maternal organs, such as lungs and the brain. Recent studies established an association between recurrent HMs and mutations in Nlrp7 gene. NLRP7 is a member of a family of proteins involved in inflammatory processes. Nevertheless, its role and biological functions remain to be elucidated. Using normal (HTR) and choriocarcinoma (JEG3) trophoblast cell lines, we characterized the role of NLRP7 in the control of key parameters of placental tumor development. Time lapse techniques were used to assess cell proliferation, migration and invasion.

Using a distinctive cohort of normal, HM, and choriocarcinoma placental tissue and sera, we compared by immunohistochemistry and RT-qPCR the levels of NLRP7 expression. Sera was used to compare the inflammatory status in these cohorts.

The in vitro study, demonstrated that NLRP7 is overexpressed in tumor cell lines and that its expression is up-regulated by hypoxia and b-hCG, two parameters that are associated to choriocarcinoma progression. Using siRNA strategy, we demonstrated that NLRP7 controls trophoblast proliferation, migration and invasion in 2D and 3D culture systems.

The clinical study, demonstrated that NLRP7 protein was highly expressed in placentas collected from HM, and choriocarcinoma patients. Analysis of the inflammatory status of these cohorts showed strong deregulations in key circulating cytokines.

Altogether our results demonstrate that NLRP7 controls key parameters of tumor placental development and bring new insights into the mechanisms that are associated to choriocarcinoma progression.