CHI3L1 features a (β/α)₈-barrel fold with a β+α domain insertion, enabling interactions with multiple receptors and extracellular components . Key binding partners include:
CHI3L1 promotes tumorigenesis through:
Cell proliferation: Activation of MAPK and PI3K pathways in glioblastoma, colon cancer, and gastric cancers
Metastasis: Upregulation of MMP-9 and IL-8, enhancing ECM degradation and angiogenesis
Immune evasion: Polarization of Th2 cells and suppression of cytotoxic T lymphocytes
Elevated serum CHI3L1 correlates with poor prognosis in metastatic cancers (HR = 2.4, 95% CI: 1.8–3.1) .
In asthma and rheumatoid arthritis, CHI3L1 drives:
CHI3L1 antibodies inhibit pathological processes by:
Recent methodologies include:
Affinity chromatography: Used to isolate chitin-binding proteins like CHI3L1 with 70% yield
Mutagenesis screens: A138D/L140E substitutions enhance binding specificity to chitin oligomers
Glycoarray profiling: Identifies cross-reactivity risks with LacdiNAc structures
Key limitations include:
Receptor redundancy: Co-expression of IL-13Rα2, TMEM219, and CD44 complicates targeting
Species variability: Murine models underrepresent human CHI3L1-IL-13Rα2 interactions
Ongoing research focuses on bispecific antibodies and CAR-T cells engineered against CHI3L1-positive stroma .