Toll-like receptor 4 selective inhibition in medullar microenvironment alters multiple myeloma cell growth - Université Toulouse III - Paul Sabatier - Toulouse INP Accéder directement au contenu
Article Dans Une Revue Blood Advances Année : 2022

Toll-like receptor 4 selective inhibition in medullar microenvironment alters multiple myeloma cell growth

Malik Hamaidia
Philippe Bourin

Résumé

Abstract Bone marrow (BM) mesenchymal stromal cells (MSCs) are abnormal in multiple myeloma (MM) and play a critical role by promoting growth, survival, and drug resistance of MM cells. We observed higher Toll-like receptor 4 (TLR4) gene expression in MM MSCs than in MSCs from healthy donors. At the clinical level, we highlighted that TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, we reasoned that the TLR4 axis is pivotal in MM by increasing the protumor activity of MSCs. Challenging primary MSCs with TLR4 agonists increased the expression of CD54 and interleukin-6 (IL-6), 2 factors directly implicated in MM MSC-MM cell crosstalk. Then, we evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro with MSC-MM cell coculture and in vivo with the Vk*MYC mouse model. Selective inhibition of TLR4 specifically reduced the MM MSC ability to support the growth of MM cells in an IL-6-dependent manner and delayed the development of MM in the Vk*MYC mouse model by altering the early disease phase in vivo. For the first time, we demonstrate that specific targeting of the pathological BM microenvironment via TLR4 signaling could be an innovative approach to alter MM pathology development.
Fichier principal
Vignette du fichier
Lemaitre_2021.pdf (1.16 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY NC ND - Paternité - Pas d'utilisation commerciale - Pas de modification

Dates et versions

hal-04569566 , version 1 (06-05-2024)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Léa Lemaitre, Malik Hamaidia, Jean-Gérard Descamps, Laura Do Souto Ferreira, Marie-Véronique Joubert, et al.. Toll-like receptor 4 selective inhibition in medullar microenvironment alters multiple myeloma cell growth. Blood Advances, 2022, 6 (2), pp.672 - 678. ⟨10.1182/bloodadvances.2020003704⟩. ⟨hal-04569566⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More