Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor
Bone marrow stromal cells (BMSCs) strongly contribute to multiple myeloma (MM) progression, promoting the survival and growth of malignant plasma cells (PCs). However, the possible impact of these cells on the immune-mediated recognition of MM cells remains largely unknown. DNAM-1 activating recepto...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/2/440 |
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| author | Abdelilah Mekhloufi Andrea Kosta Helena Stabile Rosa Molfetta Alessandra Zingoni Alessandra Soriani Marco Cippitelli Rossella Paolini Angela Gismondi Maria Rosaria Ricciardi Maria Teresa Petrucci Laura Masuelli Giulio Caracciolo Sara Palchetti Angela Santoni Cinzia Fionda |
| author_facet | Abdelilah Mekhloufi Andrea Kosta Helena Stabile Rosa Molfetta Alessandra Zingoni Alessandra Soriani Marco Cippitelli Rossella Paolini Angela Gismondi Maria Rosaria Ricciardi Maria Teresa Petrucci Laura Masuelli Giulio Caracciolo Sara Palchetti Angela Santoni Cinzia Fionda |
| author_sort | Abdelilah Mekhloufi |
| collection | DOAJ |
| description | Bone marrow stromal cells (BMSCs) strongly contribute to multiple myeloma (MM) progression, promoting the survival and growth of malignant plasma cells (PCs). However, the possible impact of these cells on the immune-mediated recognition of MM cells remains largely unknown. DNAM-1 activating receptor plays a prominent role in NK cell anti-MM response engaging the ligands poliovirus receptor (PVR) and nectin-2 on malignant PCs. Here, we analysed the role of MM patient-derived BMSCs in the regulation of PVR expression. We found that BMSCs enhance PVR surface expression on MM cells and promote their NK cell-mediated recognition. PVR upregulation occurs at transcriptional level and involves NF-kB transcription factor activation by BMSC-derived soluble factors. Indeed, overexpression of a dominant-negative mutant of IKBα blocked PVR upregulation. IL-8 plays a prominent role in these mechanisms since blockade of CXCR1/2 receptors as well as depletion of the cytokine via RNA interference prevents the enhancement of PVR expression by BMSC-derived conditioned medium. Interestingly, IL-8 is associated with stromal microvesicles which are also required for PVR upregulation via CXCR1/CXCR2 signaling activation. Our findings identify BMSCs as regulators of NK cell anti-MM response and contribute to define novel molecular pathways involved in the regulation of PVR expression in cancer cells. |
| first_indexed | 2024-03-12T07:51:59Z |
| format | Article |
| id | doaj.art-9625c38afd684b60871209b34f067daa |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:51:59Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9625c38afd684b60871209b34f067daa2023-09-02T20:32:44ZengMDPI AGCancers2072-66942020-02-0112244010.3390/cancers12020440cancers12020440Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription FactorAbdelilah Mekhloufi0Andrea Kosta1Helena Stabile2Rosa Molfetta3Alessandra Zingoni4Alessandra Soriani5Marco Cippitelli6Rossella Paolini7Angela Gismondi8Maria Rosaria Ricciardi9Maria Teresa Petrucci10Laura Masuelli11Giulio Caracciolo12Sara Palchetti13Angela Santoni14Cinzia Fionda15Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDivision of Hematology, Department of Translational Medicine and Precision, Sapienza University of Rome, 00161 Rome, ItalyDivision of Hematology, Department of Translational Medicine and Precision, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, ItalyBone marrow stromal cells (BMSCs) strongly contribute to multiple myeloma (MM) progression, promoting the survival and growth of malignant plasma cells (PCs). However, the possible impact of these cells on the immune-mediated recognition of MM cells remains largely unknown. DNAM-1 activating receptor plays a prominent role in NK cell anti-MM response engaging the ligands poliovirus receptor (PVR) and nectin-2 on malignant PCs. Here, we analysed the role of MM patient-derived BMSCs in the regulation of PVR expression. We found that BMSCs enhance PVR surface expression on MM cells and promote their NK cell-mediated recognition. PVR upregulation occurs at transcriptional level and involves NF-kB transcription factor activation by BMSC-derived soluble factors. Indeed, overexpression of a dominant-negative mutant of IKBα blocked PVR upregulation. IL-8 plays a prominent role in these mechanisms since blockade of CXCR1/2 receptors as well as depletion of the cytokine via RNA interference prevents the enhancement of PVR expression by BMSC-derived conditioned medium. Interestingly, IL-8 is associated with stromal microvesicles which are also required for PVR upregulation via CXCR1/CXCR2 signaling activation. Our findings identify BMSCs as regulators of NK cell anti-MM response and contribute to define novel molecular pathways involved in the regulation of PVR expression in cancer cells.https://www.mdpi.com/2072-6694/12/2/440pvrmultiple myelomanatural killer cellsil-8bone marrow stromal cells |
| spellingShingle | Abdelilah Mekhloufi Andrea Kosta Helena Stabile Rosa Molfetta Alessandra Zingoni Alessandra Soriani Marco Cippitelli Rossella Paolini Angela Gismondi Maria Rosaria Ricciardi Maria Teresa Petrucci Laura Masuelli Giulio Caracciolo Sara Palchetti Angela Santoni Cinzia Fionda Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor Cancers pvr multiple myeloma natural killer cells il-8 bone marrow stromal cells |
| title | Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor |
| title_full | Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor |
| title_fullStr | Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor |
| title_full_unstemmed | Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor |
| title_short | Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor |
| title_sort | bone marrow stromal cell derived il 8 upregulates pvr expression on multiple myeloma cells via nf kb transcription factor |
| topic | pvr multiple myeloma natural killer cells il-8 bone marrow stromal cells |
| url | https://www.mdpi.com/2072-6694/12/2/440 |
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