PDF(Pubmed)
Abstract：
Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.
摘要：
肿瘤来源的外泌体与器官驻留细胞结合，在局部免疫微环境重塑过程中激活S100分子。然而,关于器官驻留细胞S100A10如何介导癌症转移进展知之甚少。这里,我们提供了S100A10在调节肺免疫微环境和癌症转移中起重要作用的证据。S100A10缺陷小鼠减少了肺癌转移。此外，通过肿瘤来源的外泌体激活肺成纤维细胞中的S100A10增加了CXCL1和CXCL8趋化因子的表达，伴随着骨髓来源的抑制细胞（MDSC）募集。S100A10抑制剂如1-取代的-4-芳酰基-3-羟基-5-苯基-1H-5-吡咯-2(5H)-酮在体内抑制肺转移。我们的发现强调了S100A10在驱动MDSC募集中的关键作用，以重塑肺免疫微环境并提供潜在的治疗靶标来阻断癌症向肺部的转移。
