| Title: |
Mast cells act as pro-angiogenic and pro-tumorigenic players in pituitary gonadotroph tumors |
| Authors: |
Ilie, Mirela-Diana; Flores-Martínez, Álvaro; Chanal, Marie; Lepetit, Maxime; Samson, Benoit; Lehiani, Ayoub; Vasiljevic, Alexandre; Chinezu, Laura; Jouanneau, Emmanuel; Bernard, David; Gandrillon, Olivier; Picard, Franck; Raverot, Gérald; Bertolino, Philippe |
| Contributors: |
Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL); Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Hospices Civils de Lyon (HCL); George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures (UMFST); Systèmes de cellules avec interactions multi-échelles (MUSICS); Institut Camille Jordan (ICJ); École Centrale de Lyon (ECL); Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon); Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL); Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239); Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Inria de Lyon; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria); Institut National de la Santé et de la Recherche Médicale (INSERM); ANR-23-CE45-0017,SpaceTranscriptomiX,Méthodes d'apprentissage automatique pour identifier les réseaux d'expression spatiale et comprendre les interactions tumeur-microenvironnement des adénomes hypophysaires.(2023); ANR-17-CONV-0002,PLASCAN,Institut François Rabelais pour la recherche multidisciplinaire sur le cancer(2017); ANR-18-CE45-0023,SingleStatOmics,Statistique et Apprentissage pour la génomique en cellules uniques(2018); ANR-22-PESN-0002,AI4scMED,MultiScale AI for SingleCell-Based Precision Medicine(2022) |
| Source: |
ISSN: 1522-8517. |
| Publisher Information: |
CCSD; Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
mast cells tumor microenvironment (TME) gonadotroph adenomas single-cell transcriptomics spatial transcriptomics; mast cells; tumor microenvironment (TME); gonadotroph adenomas; single-cell transcriptomics; spatial transcriptomics; [SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; Abstract Background The tumor microenvironment (TME) represents a promising avenue to understand gonadotroph tumors and develop therapeutic tools. Here, we aimed to gain insight into the tumorigenesis mechanisms driven by the gonadotoph TME. Methods Single-cell and spatial-omics were combined with histological analysis. Mice engrafted with tumor cells were used for functional validation. Results using single-cell and spatial transcriptomic data from gonadotroph tumors and normal tissues, we identified mast cells in the microenvironment of gonadotroph tumors and confirmed their physical and functional interaction with endothelial cells. Quantification of mast cells in 40 patients suggested their pro-tumoral role as tumors relapsing after surgery harbored more mast cells. More interestingly, the distribution of mast cells was associated with the presence of a higher number of blood vessels, with an increased microvessel density (MVD), and with blood vessels with thicker walls. Ligand-receptor network analysis highlighted VEGFA as a modulator of mast/endothelial cell communication, a result confirmed by the identification of intratumoral mast cells expressing VEGFA in mouse and human gonadotroph tumors. Finally, using mice engrafted with gonadotroph tumor cells, we demonstrated that the depletion of mast cells reduces tumor volume through increased apoptosis. These observations were associated with increased hemorrhagic areas and a significant reduction of the number of blood vessels and MVD as evidenced in human gonadotroph tumors. Conclusion we demonstrate that mast cells represent a new actor of the gonadotroph TME, and highlight their pro-angiogenic and pro-tumorigenic roles as potential targets for the therapeutic treatment of gonadotroph tumors. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/neuonc/noaf241 |
| Availability: |
https://hal.science/hal-05328726; https://hal.science/hal-05328726v1/document; https://hal.science/hal-05328726v1/file/noaf241.pdf; https://doi.org/10.1093/neuonc/noaf241 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.9BF94DBA |
| Database: |
BASE |