Characterization of canine normal tissue- and tumor-derived chitinase 3-like 1

Canine transmissible venereal tumor (CTVT) is a unique tumor model for studying tumor/host immunity interaction. A progressive growing stage (P phase) followed by tumor regression (R phase) is the typical trait of this tumor with which a complicated gene-expressing network is involved to regulate tumor progression or remission. Previously, the canine chitinase 3-like 1 (CHI3L1) gene was found up-regulated in R phase CTVT. Since CHI3L1 is now mostly considered to relate to tumor malignancy or poor prognosis, we intend to inspect the role of canine CHI3L1 in CTVT. In this study, the full canine CHI3L1 gene was cloned for the first time from CTVT and normal canine macrophages to reveal that no mutations were generated in tumor specimens. By alignment with CHI3L1 from other species, protein structural and functional prediction, and in vitro protein expression followed by heparin-binding bioassay, the results indicated that canine CHI3L1 is a secretory protein with heparin-binding activity and may promote immune responses against CHI3L1. Furthermore, similar to its human homologue, canine CHI3L1 also stimulated proliferation of fibroblast cells. Taken together, CHI3L1 is a multi-functional protein known to play roles in tumor progress, autoimmune diseases, and angiogenesis. Overexpression of canine CHI3L1 in regressed CTVT may disclose associations with anti-tumor immunity or interplay between tumors and their microenvironment. Characterization of canine CHI3L1 in our study has provided new inspiration for investigating cancer biology and therapy.