Attenuation of the pro-inflammatory signature of lung cancer-derived mesenchymal stromal cells by statins.
Détails
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Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_2044EA0B5E7B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Attenuation of the pro-inflammatory signature of lung cancer-derived mesenchymal stromal cells by statins.
Périodique
Cancer letters
ISSN
1872-7980 (Electronic)
ISSN-L
0304-3835
Statut éditorial
Publié
Date de publication
01/08/2020
Peer-reviewed
Oui
Volume
484
Pages
50-64
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Solid tumor growth triggers a dynamic host response, which recapitulates wound healing and defines the tumor microenvironment (TME). In addition to the action of the tumor cells themselves, the TME is maintained by a myriad of immune and stromal cell-derived soluble mediators and extracellular matrix components whose combined action supports tumor progression. However, therapeutic targeting of the TME has proven challenging because of incomplete understanding of the tumor-host crosstalk at the molecular level. Here, we investigated the crosstalk between mesenchymal stromal cells (MSCs) and primary cancer cells (PCCs) from human squamous cell lung carcinoma (SCC). We discovered that PCCs secrete CCL3 and stimulate IL-6, CCL2, ICAM-1 and VCAM-1 expression in MSCs and that the MSC-PCC crosstalk can be disrupted by the lipid-lowering drug simvastatin, which displays pleiotropic effects on cell metabolism and suppresses IL-6 and CCL2 production by MSCs and CCL3 secretion by PCCs. In addition, simvastatin inhibited spheroid formation by PCCs and negatively affected PCC survival. Our observations demonstrate that commonly used statins may be repurposed to target the TME in lung carcinoma.
Mots-clé
Aged, Aged, 80 and over, Carcinoma, Squamous Cell/genetics, Carcinoma, Squamous Cell/metabolism, Carcinoma, Squamous Cell/pathology, Cells, Cultured, Chemokine CCL2/genetics, Chemokine CCL2/metabolism, Chemokine CCL3/genetics, Chemokine CCL3/metabolism, Cytokines/genetics, Cytokines/metabolism, Female, Gene Expression/drug effects, Humans, Inflammation Mediators/metabolism, Interleukin-6/genetics, Interleukin-6/metabolism, Lung Neoplasms/genetics, Lung Neoplasms/metabolism, Lung Neoplasms/pathology, Male, Mesenchymal Stem Cells/cytology, Mesenchymal Stem Cells/drug effects, Mesenchymal Stem Cells/metabolism, Middle Aged, Simvastatin/pharmacology, Tumor Cells, Cultured, Tumor Microenvironment/drug effects, Tumor Microenvironment/genetics, CCL2, CCL3, Interleukin-6, Lung cancer, Mesenchymal stromal cells, Simvastatin
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/05/2020 16:15
Dernière modification de la notice
22/12/2021 7:08