TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion
Summary: A crucial requirement for metastasis formation in ovarian high-grade serous carcinoma (HGSC) is the disruption of the protective peritoneal mesothelium. Using co-culture systems of primary human cells, we discovered that tumor-associated NK cells induce TRAIL-dependent apoptosis in mesothel...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223024781 |
| _version_ | 1797388779788435456 |
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| author | Anna Mary Steitz Clarissa Schröder Isabel Knuth Corinna U. Keber Leah Sommerfeld Florian Finkernagel Julia M. Jansen Uwe Wagner Sabine Müller-Brüsselbach Thomas Worzfeld Magdalena Huber Vanessa M. Beutgen Johannes Graumann Elke Pogge von Strandmann Rolf Müller Silke Reinartz |
| author_facet | Anna Mary Steitz Clarissa Schröder Isabel Knuth Corinna U. Keber Leah Sommerfeld Florian Finkernagel Julia M. Jansen Uwe Wagner Sabine Müller-Brüsselbach Thomas Worzfeld Magdalena Huber Vanessa M. Beutgen Johannes Graumann Elke Pogge von Strandmann Rolf Müller Silke Reinartz |
| author_sort | Anna Mary Steitz |
| collection | DOAJ |
| description | Summary: A crucial requirement for metastasis formation in ovarian high-grade serous carcinoma (HGSC) is the disruption of the protective peritoneal mesothelium. Using co-culture systems of primary human cells, we discovered that tumor-associated NK cells induce TRAIL-dependent apoptosis in mesothelial cells via death receptors DR4 and DR5 upon encounter with activated T cells. Upregulation of TRAIL expression in NK cells concomitant with enhanced cytotoxicity toward mesothelial cells was driven predominantly by T-cell-derived TNFα, as shown by affinity proteomics-based analysis of the T cell secretome in conjunction with functional studies. Consistent with these findings, we detected apoptotic mesothelial cells in the peritoneal fluid of HGSC patients. In contrast to mesothelial cells, HGSC cells express negligible levels of both DR4 and DR5 and are TRAIL resistant, indicating cell-type-selective killing by NK cells. Our data point to a cooperative action of T and NK in breaching the mesothelial barrier in HGSC patients. |
| first_indexed | 2024-03-08T22:45:46Z |
| format | Article |
| id | doaj.art-e9c08e3135684fc89cfce67f8891a099 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:46Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-e9c08e3135684fc89cfce67f8891a0992023-12-17T06:40:39ZengElsevieriScience2589-00422023-12-012612108401TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasionAnna Mary Steitz0Clarissa Schröder1Isabel Knuth2Corinna U. Keber3Leah Sommerfeld4Florian Finkernagel5Julia M. Jansen6Uwe Wagner7Sabine Müller-Brüsselbach8Thomas Worzfeld9Magdalena Huber10Vanessa M. Beutgen11Johannes Graumann12Elke Pogge von Strandmann13Rolf Müller14Silke Reinartz15Translational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyInstitute for Pathology, Philipps University, 35043 Marburg, GermanyTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyClinic for Gynecology, Gynecological Oncology, Gynecological Endocrinology, University Hospital (UKGM), 35043 Marburg, GermanyClinic for Gynecology, Gynecological Oncology, Gynecological Endocrinology, University Hospital (UKGM), 35043 Marburg, GermanyTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyInstitute of Pharmacology, Biochemical-Pharmacological Center (BPC), Philipps University, 35043 Marburg, GermanyInstitute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, GermanyInstitute of Translational Proteomics, Philipps University, 35043 Marburg, Germany; Core Facility Translational Proteomics, Philipps University, 35043 Marburg, GermanyInstitute of Translational Proteomics, Philipps University, 35043 Marburg, Germany; Core Facility Translational Proteomics, Philipps University, 35043 Marburg, GermanyInstitute for Tumor Immunology, Center for Tumor Biology and Immunology (ZTI), Clinic for Hematology, Oncology and Immunology, Philipps University, 35043 Marburg, GermanyTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, Germany; Corresponding authorTranslational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University, 35043 Marburg, Germany; Corresponding authorSummary: A crucial requirement for metastasis formation in ovarian high-grade serous carcinoma (HGSC) is the disruption of the protective peritoneal mesothelium. Using co-culture systems of primary human cells, we discovered that tumor-associated NK cells induce TRAIL-dependent apoptosis in mesothelial cells via death receptors DR4 and DR5 upon encounter with activated T cells. Upregulation of TRAIL expression in NK cells concomitant with enhanced cytotoxicity toward mesothelial cells was driven predominantly by T-cell-derived TNFα, as shown by affinity proteomics-based analysis of the T cell secretome in conjunction with functional studies. Consistent with these findings, we detected apoptotic mesothelial cells in the peritoneal fluid of HGSC patients. In contrast to mesothelial cells, HGSC cells express negligible levels of both DR4 and DR5 and are TRAIL resistant, indicating cell-type-selective killing by NK cells. Our data point to a cooperative action of T and NK in breaching the mesothelial barrier in HGSC patients.http://www.sciencedirect.com/science/article/pii/S2589004223024781MicroenvironmentImmunologyCancer |
| spellingShingle | Anna Mary Steitz Clarissa Schröder Isabel Knuth Corinna U. Keber Leah Sommerfeld Florian Finkernagel Julia M. Jansen Uwe Wagner Sabine Müller-Brüsselbach Thomas Worzfeld Magdalena Huber Vanessa M. Beutgen Johannes Graumann Elke Pogge von Strandmann Rolf Müller Silke Reinartz TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion iScience Microenvironment Immunology Cancer |
| title | TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion |
| title_full | TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion |
| title_fullStr | TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion |
| title_full_unstemmed | TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion |
| title_short | TRAIL-dependent apoptosis of peritoneal mesothelial cells by NK cells promotes ovarian cancer invasion |
| title_sort | trail dependent apoptosis of peritoneal mesothelial cells by nk cells promotes ovarian cancer invasion |
| topic | Microenvironment Immunology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223024781 |
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