Siglec-14-LGALS3BP glycoimmune axis shapes tumor-associated macrophage polarization and confers poor outcome in colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, particularly in metastatic cases. Sialic acid, frequently overexpressed in tumors, promotes immune evasion by engaging Siglecs (Sialic acid-binding immunoglobulin-like lectins) on immune cells. Siglec-5 and Siglec-14, expressed on myeloid cells, share ligand-binding domains but have opposing signaling functions. While these paired receptors regulate macrophage immune responses against bacterial infection, their role in the tumor microenvironment remains unclear. We found that Siglec-14 expression in THP-1 macrophages, when exposed to CRC tumor-conditioned medium, induces a protumoral SPP1⁺ tumor-associated macrophage phenotype, with enrichment of angiogenic pathways. In vivo, Siglec-14-expressing macrophages pr

SUBMITTER: Lin KY 

PROVIDER: S-EPMC12706041 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature