NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment
The inflammatory gene <i>NLRP7</i> is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigat...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2999 |
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| author | Deborah Reynaud Roland Abi Nahed Nicolas Lemaitre Pierre-Adrien Bolze Wael Traboulsi Frederic Sergent Christophe Battail Odile Filhol Vincent Sapin Houssine Boufettal Pascale Hoffmann Touria Aboussaouira Padma Murthi Rima Slim Mohamed Benharouga Nadia Alfaidy |
| author_facet | Deborah Reynaud Roland Abi Nahed Nicolas Lemaitre Pierre-Adrien Bolze Wael Traboulsi Frederic Sergent Christophe Battail Odile Filhol Vincent Sapin Houssine Boufettal Pascale Hoffmann Touria Aboussaouira Padma Murthi Rima Slim Mohamed Benharouga Nadia Alfaidy |
| author_sort | Deborah Reynaud |
| collection | DOAJ |
| description | The inflammatory gene <i>NLRP7</i> is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for <i>NLRP7</i>, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC. |
| first_indexed | 2024-03-10T10:23:43Z |
| format | Article |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:23:43Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ad4c14b89e444380978098f8f1d9c1d72023-11-22T00:13:52ZengMDPI AGCancers2072-66942021-06-011312299910.3390/cancers13122999NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive MicroenvironmentDeborah Reynaud0Roland Abi Nahed1Nicolas Lemaitre2Pierre-Adrien Bolze3Wael Traboulsi4Frederic Sergent5Christophe Battail6Odile Filhol7Vincent Sapin8Houssine Boufettal9Pascale Hoffmann10Touria Aboussaouira11Padma Murthi12Rima Slim13Mohamed Benharouga14Nadia Alfaidy15Institut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceDepartment of Gynecological Surgery and Oncology, Obstetrics, French Reference Center for Gestational Trophoblastic Diseases, University Hospital Lyon Sud, University of Lyon 1, 69000 Lyon, FranceLaboratory for Immuno-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 2005, USAInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceGenetics, Reproduction and Development (GReD) Laboratory, CNRS UMR 6293, Inserm U1103, Translational Approach to Epithelial Injury and Repair Team, Clermont Auvergne University, 63000 Clermont-Ferrand, FranceObstetrics and Gynecology Department, Ibn Rochd University Hospital, Hassan 2 University, Faculty of Medicine and Pharmacy, 20360 Casablanca, MoroccoInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceObstetrics and Gynecology Department, Ibn Rochd University Hospital, Hassan 2 University, Faculty of Medicine and Pharmacy, 20360 Casablanca, MoroccoDepartment of Pharmacology, Monash Biomedicine Discovery Institute, Monash, Clayton, VIC 3168, AustraliaDepartments of Human Genetics and Obstetrics and Gynecology, McGill University Health Centre Research Institute, Montréal, QC H4A 3J1, CanadaInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale, Inserm U1292, Université Grenoble-Alpes, 38000 Grenoble, FranceThe inflammatory gene <i>NLRP7</i> is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for <i>NLRP7</i>, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.https://www.mdpi.com/2072-6694/13/12/2999choriocarcinomahydatidiform moleNLRP7tumor microenvironmentmaternal immune toleranceorthotopic model of choriocarcinoma |
| spellingShingle | Deborah Reynaud Roland Abi Nahed Nicolas Lemaitre Pierre-Adrien Bolze Wael Traboulsi Frederic Sergent Christophe Battail Odile Filhol Vincent Sapin Houssine Boufettal Pascale Hoffmann Touria Aboussaouira Padma Murthi Rima Slim Mohamed Benharouga Nadia Alfaidy NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment Cancers choriocarcinoma hydatidiform mole NLRP7 tumor microenvironment maternal immune tolerance orthotopic model of choriocarcinoma |
| title | NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment |
| title_full | NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment |
| title_fullStr | NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment |
| title_full_unstemmed | NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment |
| title_short | NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment |
| title_sort | nlrp7 promotes choriocarcinoma growth and progression through the establishment of an immunosuppressive microenvironment |
| topic | choriocarcinoma hydatidiform mole NLRP7 tumor microenvironment maternal immune tolerance orthotopic model of choriocarcinoma |
| url | https://www.mdpi.com/2072-6694/13/12/2999 |
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