Background

M2-polarized macrophages aggressively modulate the tumor microenvironment and enhance tumor cell malignancy. As intracellular molecules are released by damaged or stressed cells, damage-associated molecular patterns (DAMPs) bind to toll-like receptors (TLRs) on cells in the tumor microenvironment, inducing inflammation and epithelial-mesenchymal transition. However, recent studies on the crosstalk between DAMPs and M2-polarized macrophages (M2 macrophages) during tumor progression have not provided conclusive results.

Objective

We investigated the role of toll-like receptors (TLRs) in IL-6 production by M2 macrophages and searched for cancer cell-derived DAMPs that can activate the TLRs responsible for IL-6 production.

Results

TLR2 activation was required for IL-6 production by M2 macrophages. The malignancy of cancer cells was increased by the activation of this pathway. Cancer-derived HSP 72 acted as a ligand that stimulates the TLR2 signaling pathway in M2 macrophages, triggering IL-6 production.

Conclusion

TLR 2 stimulation in M2 macrophages enhances tumor malignancy by upregulating IL-6. Heat shock protein 72 (HSP72) is a potent TLR2 stimulator. Our findings reveal a connection between TLR2 and M2-polarized macrophages in tumor malignancy and may be useful for developing effective treatments for tumor relapse.

中文翻译：

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HSP72 是激活 M2 巨噬细胞中 Toll 样受体 2 的刺激物，导致 IL-6 介导的肿瘤恶性肿瘤

 背景

M2极化巨噬细胞积极调节肿瘤微环境并增强肿瘤细胞的恶性程度。当受损或应激细胞释放细胞内分子时，损伤相关分子模式 (DAMP) 会与肿瘤微环境中细胞上的 Toll 样受体 (TLR) 结合，诱导炎症和上皮间质转化。然而，最近关于肿瘤进展过程中 DAMP 和 M2 极化巨噬细胞（M2 巨噬细胞）之间的串扰的研究尚未提供结论性结果。

 客观的

我们研究了 Toll 样受体 (TLR) 在 M2 巨噬细胞产生 IL-6 中的作用，并寻找能够激活负责 IL-6 产生的 TLR 的癌细胞衍生的 DAMP。

 结果

M2 巨噬细胞产生 IL-6 需要 TLR2 激活。该途径的激活会增加癌细胞的恶性程度。癌症衍生的 HSP 72 作为配体刺激 M2 巨噬细胞中的 TLR2 信号通路，触发 IL-6 的产生。

 结论

M2 巨噬细胞中的 TLR 2 刺激通过上调 IL-6 增强肿瘤的恶性程度。热休克蛋白 72 (HSP72) 是一种有效的 TLR2 刺激剂。我们的研究结果揭示了肿瘤恶性肿瘤中 TLR2 和 M2 极化巨噬细胞之间的联系，可能有助于开发肿瘤复发的有效治疗方法。