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

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.

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