Fucosylated chondroitin sulfate exerts in vitro anti-tumor property through manipulating the metabolism related polarization of macrophages

  • Int J Biol Macromol. 2025 Aug;320(Pt 2):145830. doi: 10.1016/j.ijbiomac.2025.145830.
Jing Liu  1 ,  Mengqiu Hu  2 ,  Yanying Sun  2 ,  Lei Zhao  1 ,  Bin Wang  1 ,  Xiaohui Qi  3 ,  Jiaojiao Mou  4 ,  Jie Yang  5
Affiliations
  • 1. School of Pharmacy, Shandong Second Medical University, Weifang 261053, Shandong, China.
  • 2. School of Public Health, Shandong Second Medical University, Weifang 261053, Shandong, China.
  • 3. School of Life Sciences and Technology, Shandong Second Medical University, Weifang 261053, Shandong, China. Electronic address: [email protected].
  • 4. School of Public Health, Shandong Second Medical University, Weifang 261053, Shandong, China. Electronic address: [email protected].
  • 5. School of Pharmacy, Shandong Second Medical University, Weifang 261053, Shandong, China. Electronic address: [email protected].
PMID: 40633868 DOI: 10.1016/j.ijbiomac.2025.145830
Abstract

Tumor associated macrophages (TAMs) participate in the development of tumor, which was reported to dominantly be alternatively activated M2 subtype. Metabolic reprogramming of TAMs into tumor-inhibiting M1 type has shown to be a promising treatment strategy. In this study, we firstly demonstrated fucosylated chondroitin sulfate isolated from sea cucumber Stichopus chloronotus (fCS-Sc) exerted anti-tumor effects. fCS-Sc intervened the metabolism-polarization crosstalk of macrophages and reprogrammed M2 RAW264.7 cells to M1 subtype. fCS-Sc converted IL-4 and IL-13 mediated M2-like RAW264.7 cells to M1 subtype and enhanced the M1-like anti-tumor immunity via suppressing STAT6 signaling and promoting TLRs-NF-κB pathway. The reprogramming effect of fCS-Sc on M2 subtype macrophages were closely related to its metabolism. fCS-Sc markedly elevated the glycolytic pathway and down-regulated fatty acid oxidation pathway. Furthermore, the co-culture assay of M2 subtype RAW264.7 cells and 4 T1 cells demonstrated that fCS-Sc reprogrammed the M2 macrophages to M1 subtype and facilitated its tumor-killing ability. This study will contribute to the application of fCS-Sc as an ancillary drug in anti-tumor treatments.

Keywords
Anti-tumor property; Cell metabolism; Fucosylated chondroitin sulfate; Polarization of macrophages.
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