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

Abstract

The human and mouse orthologues/encode a chitinase-related protein that is catalytically inactive. It is overexpressed in multiple inflammatory disorders and cancers and is thought to be pro-inflammatory and immune modulatory, but its role in tumorigenesis is unclear. Nevertheless, it has been proposed as a therapeutic target. To explore this, we have used Chil1 knockout compared with Chil1 WT mice, in combination with a transgenic mouse model (encoding the latent membrane protein-1 of EBV) of carcinoma-prone chronic skin inflammation. The data reveal that although high levels of Chil1 are pro-inflammatory, this can ameliorate the consequent tissue damage. Moreover, although high-level Chil1 promotes carcinoma growth, physiological levels inhibit the formation of papillomatous lesions and similarly inhibit the growth of tumours from transplanted cells. Furthermore, tumours arising in the Chil1 knockout mice showed reduced leukocyte infiltration, consistent with an impaired anti-tumour response. These dual roles warrant caution in developing and exploring therapeutic drugs that might abrogate Chil1 expression or effect.