bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Abstract Tumor-associated macrophages (TAMs) form functionally diverse populations of innate immune cells in the tumor microenvironment (TME). Pro- and anti-inflammatory TAMs are central to cancer progression by shaping inflammation (im)balance, but it remains unknown if polarization-induced remodeling TAM glycocalyx critical for cellular communication occurs within TME. Taking a systems glycobiology approach, we here firstly used cell surface-focused glycomics lectin flow cytometry ex vivo polarized monocyte-derived demonstrate profound sialyl linkage switching surface N -glycome pro-inflammatory (α2,3-sialo-favored) (α2,6-sialo-dominant) macrophages. In contrast, no alterations sialylation were observed O -glycome. ST6GAL1 that modifies -glycans with α2,6-sialylation was elevated compared levels providing mechanistic basis switching, which supported silencing. Interestingly, SNA-focused cytochemistry revealed dense networks dynamic α2,6-sialylated protein-based nanotubules forming inter-connecting structures absent Temporal silencing caused nanotubule disintegration as evidenced SNA biotin fluorescence microscopy. Moreover, live recordings cultured without colorectal (CRC) showed reduced macrophage motility, attenuated inter-macrophage macrophage-CRC interactions diminished CRC proliferation upon disruption indicating functional roles nanotubules. Finally, recapitulated pro- from tissues patients advanced CRC. We report on consequences accompanying polarization.

Language: Английский