Extracellular HSP90α Induces MyD88-IRAK Complex-Associated IKKα/β-NF-κB/IRF3 and JAK2/TYK2-STAT-3 Signaling in Macrophages for Tumor-Promoting M2-Polarization.

ABSTRACT: M2-polarization and the tumoricidal to tumor-promoting transition are commonly observed with tumor-infiltrating macrophages after interplay with cancer cells or/and other stroma cells. Our previous study indicated that macrophage M2-polarization can be induced by extracellular HSP90α (eHSP90α) secreted from endothelial-to-mesenchymal transition-derived cancer-associated fibroblasts. To extend the finding, we herein validated that eHSP90α-induced M2-polarized macrophages exhibited a tumor-promoting activity and the promoted tumor tissues had significant increases in microvascular density but decreases in CD4+ T-cell level. We further investigated the signaling pathways occurring in eHSP90α-stimulated macrophages. When macrophages were exposed to eHSP90α, CD91 and toll-like receptor 4 (TLR4)

SUBMITTER: Fan CS 

PROVIDER: S-EPMC8774043 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature