S100A10 promotes cancer metastasis via recruitment of MDSCs within the lungs

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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.
Funding Information
  • Innovation Capability Support Program of Shaanxi (2020TD-046)
  • Key Research and Development Program of Shaanxi (2019SF-145)
  • The First Affiliated Hospital of Xian Jiaotong University College of Medicine Foundation (2022 MS-01)
  • The National Natural Science Foundation of China (82373389 82173023)

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