Tumor-derived IL-6 promotes chordoma invasion by stimulating tumor-associated macrophages M2 polarization and TNFα secretion.

Autor: Chen Y; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Guo Y; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Li S; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Xu J; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Zhao C; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Wang J; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Yang J; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Ning W; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Qu Y; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Zhang M; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China., Wang S; CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China. Electronic address: sdwang@ibp.ac.cn., Zhang H; Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China. Electronic address: zhanghongwei@ccmu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 1), pp. 113315. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.intimp.2024.113315
Abstrakt: Aims: Chordoma is a rare and aggressive bone tumor with high-recurrence and lack of effective treatment methods. Tumor associated macrophages (TAMs) are abundant in tumor microenvironment (TME) and polarize toward M2 in chordoma. It has been observed that the high proportion of M2 cells is associated with chordoma rapid progression. However, the mechanism of TAMs polarization and promotion to tumor progression in chordoma is still unclear. The is an urgent need for further research.
Materials and Methods: Flow cytometry and immunohistochemical staining was used to detect the degree of macrophages infiltration in chordoma. A co-culture model of chordoma cells and macrophages was established in vitro to investigate the effects of their interaction on cell function, cytokine secretion, and RNA transcriptome expression.
Key Findings: In this study, we found M2 macrophage was predominantly abundant immune cell population in chordoma, and its proportion was associated with the degree of bone destruction. We demonstrated that interleukin 6 (IL-6) derived from chordoma cells could induce TAMs polarization by activating STAT3 phosphorylation, and TAMs could enhance chordoma cells migration and invasion through TNFα/NF-κB pathway. The interaction of chordoma cells and TAMs could promote the bone destruction-related factor Cathepsin B (CTSB) and inhibitory immune checkpoints expression. We also confirmed blocking IL-6/STAT3 pathway could significantly attenuate the M2 polarization of TAMs and decrease the secretion of TNFα.
Significance: This study illustrates the dynamics between chordoma cells and TAMs in promoting chordoma invasion and suggests that IL-6/STAT3 pathway is a potential therapeutic target to reduce TAM-induced chordoma invasion.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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