Up-regulated chitinase-like protein-1 promotes tumour growth while physiological levels are protective

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Human and mouse orthologues CHI3L1/Chil1 encode a catalytically inactive chitinase-related protein.
• CHI3L1 is overexpressed in inflammatory disorders and cancers, with proposed pro-inflammatory and immune-modulatory roles.
• Its specific function in tumorigenesis remains unclear, despite being a potential therapeutic target.

Purpose of the Study:

• To investigate the role of Chil1 in tumorigenesis using a knockout mouse model.
• To examine the effects of Chil1 on chronic skin inflammation and carcinoma development.
• To clarify the dual functions of Chil1 in cancer and inflammation.

Main Methods:

• Utilized Chil1 knockout (KO) mice and wild-type (WT) mice.
• Employed a transgenic mouse model of carcinoma-prone chronic skin inflammation (encoding EBV latent membrane protein-1).
• Compared tumor development and leukocyte infiltration between Chil1 KO and WT mice.

Main Results:

• High levels of Chil1 were found to be pro-inflammatory but ameliorated tissue damage.
• High-level Chil1 promoted carcinoma growth, whereas physiological levels inhibited papillomatous lesions and transplanted tumor growth.
• Tumors in Chil1 KO mice exhibited reduced leukocyte infiltration, indicating impaired anti-tumor response.

Conclusions:

• Chil1 exhibits dual roles in cancer, promoting inflammation and tumor growth at high levels while inhibiting lesion formation at physiological levels.
• The impaired anti-tumor response in Chil1 KO mice suggests a complex interaction with the immune system.
• Caution is advised when developing therapeutics targeting CHI3L1 expression or activity due to its multifaceted roles.