NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway
Background: Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). <i>NLRP7</i> is the major gene responsible for recurrent HM and is involved in the innate immune response, inflammation and apoptosis. NLRP7...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/6/857 |
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| author | Déborah Reynaud Nadia Alfaidy Constance Collet Nicolas Lemaitre Frederic Sergent Céline Miege Emmanuelle Soleilhac Alaa Al Assi Padma Murthi Gilles Courtois Marie-Odile Fauvarque Rima Slim Mohamed Benharouga Roland Abi Nahed |
| author_facet | Déborah Reynaud Nadia Alfaidy Constance Collet Nicolas Lemaitre Frederic Sergent Céline Miege Emmanuelle Soleilhac Alaa Al Assi Padma Murthi Gilles Courtois Marie-Odile Fauvarque Rima Slim Mohamed Benharouga Roland Abi Nahed |
| author_sort | Déborah Reynaud |
| collection | DOAJ |
| description | Background: Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). <i>NLRP7</i> is the major gene responsible for recurrent HM and is involved in the innate immune response, inflammation and apoptosis. NLRP7 can function in an inflammasome-dependent or -independent pathway. Recently, we have demonstrated that <i>NLRP7</i> is highly expressed in GC tumor cells and contributes to their tumorigenesis. However, the underlying mechanisms are still unknown. Here, we investigated the mechanism by which NLRP7 controls these processes in malignant (JEG-3) and non-tumor (HTR8/SVneo) trophoblastic cells. Cell survival, dedifferentiation, camouflage, and aggressiveness were compared between normal JEG-3 cells or knockdown for <i>NLRP7,</i> JEG-3 Sh <i>NLRP7</i>. In addition, HTR8/SVneo cells overexpressing <i>NLRP7</i> were used to determine the impact of <i>NLRP7</i> overexpression on non-tumor cells. NLRP7 involvement in tumor cell growth and tolerance was further characterized in vivo using the metastatic mouse model of GC. Results: We demonstrate that NLRP7 (i) functions in an inflammasome-dependent and -independent manners in HTR8/SVneo and JEG-3 cells, respectively; (ii) differentially regulates the activity of NF-κB in tumor and non-tumor cells; (iii) increases malignant cell survival, dedifferentiation, and camouflage; and (iv) facilitates tumor cells colonization of the lungs in the preclinical model of GC. Conclusions: This study demonstrates for the first time the mechanism by which NLRP7, independently of its inflammasome machinery, contributes to GC growth and tumorigenesis. The clinical relevance of NLRP7 in this rare cancer highlights its potential therapeutic promise as a molecular target to treat resistant GC patients. |
| first_indexed | 2024-03-11T06:48:10Z |
| format | Article |
| id | doaj.art-f4b51aa30b714a239a34a543de1d478d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:48:10Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f4b51aa30b714a239a34a543de1d478d2023-11-17T10:12:51ZengMDPI AGCells2073-44092023-03-0112685710.3390/cells12060857NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent PathwayDéborah Reynaud0Nadia Alfaidy1Constance Collet2Nicolas Lemaitre3Frederic Sergent4Céline Miege5Emmanuelle Soleilhac6Alaa Al Assi7Padma Murthi8Gilles Courtois9Marie-Odile Fauvarque10Rima Slim11Mohamed Benharouga12Roland Abi Nahed13Institut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceUniversity Grenoble Alpes, Inserm, CEA, UA13 BGE, 38000 Grenoble, FranceLaboratory of Fundamental and Applied Bioenergetics (LBFA), Univeristy Grenoble Alpes, Inserm, 38000 Grenoble, FranceDepartment of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne VIC 3800, AustraliaUniversity Grenoble Alpes, Inserm, CEA, UA13 BGE, 38000 Grenoble, FranceUniversity Grenoble Alpes, Inserm, CEA, UA13 BGE, 38000 Grenoble, FranceDepartments 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 U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie pour la Santé, 38043 Grenoble, FranceBackground: Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). <i>NLRP7</i> is the major gene responsible for recurrent HM and is involved in the innate immune response, inflammation and apoptosis. NLRP7 can function in an inflammasome-dependent or -independent pathway. Recently, we have demonstrated that <i>NLRP7</i> is highly expressed in GC tumor cells and contributes to their tumorigenesis. However, the underlying mechanisms are still unknown. Here, we investigated the mechanism by which NLRP7 controls these processes in malignant (JEG-3) and non-tumor (HTR8/SVneo) trophoblastic cells. Cell survival, dedifferentiation, camouflage, and aggressiveness were compared between normal JEG-3 cells or knockdown for <i>NLRP7,</i> JEG-3 Sh <i>NLRP7</i>. In addition, HTR8/SVneo cells overexpressing <i>NLRP7</i> were used to determine the impact of <i>NLRP7</i> overexpression on non-tumor cells. NLRP7 involvement in tumor cell growth and tolerance was further characterized in vivo using the metastatic mouse model of GC. Results: We demonstrate that NLRP7 (i) functions in an inflammasome-dependent and -independent manners in HTR8/SVneo and JEG-3 cells, respectively; (ii) differentially regulates the activity of NF-κB in tumor and non-tumor cells; (iii) increases malignant cell survival, dedifferentiation, and camouflage; and (iv) facilitates tumor cells colonization of the lungs in the preclinical model of GC. Conclusions: This study demonstrates for the first time the mechanism by which NLRP7, independently of its inflammasome machinery, contributes to GC growth and tumorigenesis. The clinical relevance of NLRP7 in this rare cancer highlights its potential therapeutic promise as a molecular target to treat resistant GC patients.https://www.mdpi.com/2073-4409/12/6/857NLRP7inflammasomegestational choriocarcinomacamouflageNF-κBcancer |
| spellingShingle | Déborah Reynaud Nadia Alfaidy Constance Collet Nicolas Lemaitre Frederic Sergent Céline Miege Emmanuelle Soleilhac Alaa Al Assi Padma Murthi Gilles Courtois Marie-Odile Fauvarque Rima Slim Mohamed Benharouga Roland Abi Nahed NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway Cells NLRP7 inflammasome gestational choriocarcinoma camouflage NF-κB cancer |
| title | NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway |
| title_full | NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway |
| title_fullStr | NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway |
| title_full_unstemmed | NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway |
| title_short | NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway |
| title_sort | nlrp7 enhances choriocarcinoma cell survival and camouflage in an inflammasome independent pathway |
| topic | NLRP7 inflammasome gestational choriocarcinoma camouflage NF-κB cancer |
| url | https://www.mdpi.com/2073-4409/12/6/857 |
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