Endothelial calcium firing mediates the extravasation of metastatic tumor cells
Summary: Metastatic dissemination is driven by genetic, biochemical, and biophysical cues that favor the distant colonization of organs and the formation of life-threatening secondary tumors. We have previously demonstrated that endothelial cells (ECs) actively remodel during extravasation by enwrap...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224029171 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832595825570611200 |
|---|---|
| author | Marina Peralta Amandine Dupas Annabel Larnicol Olivier Lefebvre Ruchi Goswami Tristan Stemmelen Anne Molitor Raphael Carapito Salvatore Girardo Naël Osmani Jacky G. Goetz |
| author_facet | Marina Peralta Amandine Dupas Annabel Larnicol Olivier Lefebvre Ruchi Goswami Tristan Stemmelen Anne Molitor Raphael Carapito Salvatore Girardo Naël Osmani Jacky G. Goetz |
| author_sort | Marina Peralta |
| collection | DOAJ |
| description | Summary: Metastatic dissemination is driven by genetic, biochemical, and biophysical cues that favor the distant colonization of organs and the formation of life-threatening secondary tumors. We have previously demonstrated that endothelial cells (ECs) actively remodel during extravasation by enwrapping arrested tumor cells (TCs) and extruding them from the vascular lumen while maintaining perfusion. In this work, we dissect the cellular and molecular mechanisms driving endothelial remodeling. Using high-resolution intravital imaging in zebrafish embryos, we demonstrate that the actomyosin network of ECs controls tissue remodeling and subsequent TC extravasation. Furthermore, we uncovered that this cytoskeletal remodeling is driven by altered endothelial-calcium (Ca2+) signaling caused by arrested TCs. Accordingly, we demonstrated that the inhibition of voltage-dependent calcium L-type channels impairs extravasation. Lastly, we identified P2X4, TRP, and Piezo1 mechano-gated Ca2+ channels as key mediators of the process. These results further highlight the central role of endothelial remodeling during the extravasation of TCs and open avenues for successful therapeutic targeting. |
| format | Article |
| id | doaj-art-d77ac51d271044548b2bcfc207531cb8 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-d77ac51d271044548b2bcfc207531cb82025-01-18T05:05:04ZengElsevieriScience2589-00422025-02-01282111690Endothelial calcium firing mediates the extravasation of metastatic tumor cellsMarina Peralta0Amandine Dupas1Annabel Larnicol2Olivier Lefebvre3Ruchi Goswami4Tristan Stemmelen5Anne Molitor6Raphael Carapito7Salvatore Girardo8Naël Osmani9Jacky G. Goetz10Tumor Biomechanics lab, INSERM UMR_S1109, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Corresponding authorTumor Biomechanics lab, INSERM UMR_S1109, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceTumor Biomechanics lab, INSERM UMR_S1109, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceTumor Biomechanics lab, INSERM UMR_S1109, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, FranceMax Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, GermanyUniversité de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Laboratoire d’ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Strasbourg, France; Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1 Place de l'Hôpital, 67091 Strasbourg, FranceLaboratoire d’ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Strasbourg, FranceUniversité de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Laboratoire d’ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Strasbourg, France; Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1 Place de l'Hôpital, 67091 Strasbourg, FranceMax Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, GermanyTumor Biomechanics lab, INSERM UMR_S1109, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Corresponding authorTumor Biomechanics lab, INSERM UMR_S1109, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Corresponding authorSummary: Metastatic dissemination is driven by genetic, biochemical, and biophysical cues that favor the distant colonization of organs and the formation of life-threatening secondary tumors. We have previously demonstrated that endothelial cells (ECs) actively remodel during extravasation by enwrapping arrested tumor cells (TCs) and extruding them from the vascular lumen while maintaining perfusion. In this work, we dissect the cellular and molecular mechanisms driving endothelial remodeling. Using high-resolution intravital imaging in zebrafish embryos, we demonstrate that the actomyosin network of ECs controls tissue remodeling and subsequent TC extravasation. Furthermore, we uncovered that this cytoskeletal remodeling is driven by altered endothelial-calcium (Ca2+) signaling caused by arrested TCs. Accordingly, we demonstrated that the inhibition of voltage-dependent calcium L-type channels impairs extravasation. Lastly, we identified P2X4, TRP, and Piezo1 mechano-gated Ca2+ channels as key mediators of the process. These results further highlight the central role of endothelial remodeling during the extravasation of TCs and open avenues for successful therapeutic targeting.http://www.sciencedirect.com/science/article/pii/S2589004224029171cell biologyFunctional aspects of cell biologycancer |
| spellingShingle | Marina Peralta Amandine Dupas Annabel Larnicol Olivier Lefebvre Ruchi Goswami Tristan Stemmelen Anne Molitor Raphael Carapito Salvatore Girardo Naël Osmani Jacky G. Goetz Endothelial calcium firing mediates the extravasation of metastatic tumor cells iScience cell biology Functional aspects of cell biology cancer |
| title | Endothelial calcium firing mediates the extravasation of metastatic tumor cells |
| title_full | Endothelial calcium firing mediates the extravasation of metastatic tumor cells |
| title_fullStr | Endothelial calcium firing mediates the extravasation of metastatic tumor cells |
| title_full_unstemmed | Endothelial calcium firing mediates the extravasation of metastatic tumor cells |
| title_short | Endothelial calcium firing mediates the extravasation of metastatic tumor cells |
| title_sort | endothelial calcium firing mediates the extravasation of metastatic tumor cells |
| topic | cell biology Functional aspects of cell biology cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224029171 |
| work_keys_str_mv | AT marinaperalta endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT amandinedupas endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT annabellarnicol endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT olivierlefebvre endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT ruchigoswami endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT tristanstemmelen endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT annemolitor endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT raphaelcarapito endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT salvatoregirardo endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT naelosmani endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells AT jackyggoetz endothelialcalciumfiringmediatestheextravasationofmetastatictumorcells |