Role Of Chitinase-like Proteins Research Articles

CHITINASE-LIKE PROTEINS AS PROMISING MARKERS IN CANCER PATIENTS

In the present review we collected the main studies regarding the role of chitinase-like proteins (CLPs), belonging to the family of Glyco_18 domain-containing proteins, in different cancers. In humans, 3 chitinaselike proteins have been identified: YKL-40 (CHI3L1), YKL-39 (CHI3L2) and stabilin-1-interacting chitinase-like protein (SI-CLP). CLPs are produced by several types of cells and combine the properties of cytokines and growth factors. The high levels of CLPs were identified in the circulation of the patients with inflammatory diseases and various types of tumors. We highlighted the main known functions of CLPs in normal and pathological conditions, their contribution to metastasis development, angiogenesis, invasion and other processes in cancer, the correlation of the levels of CLPs with tumour progression. Our data also contribute to the understanding of question how CLP could be useful for cancer patient benefit.

Role of chitinase-like proteins in cancer.

Chitinase-like proteins (CLPs) are lectins combining properties of cytokines and growth factors. Human CLPs include YKL-40, YKL-39 and SI-CLP that are secreted by cancer cells, macrophages, neutrophils, synoviocytes, chondrocytes and other cells. The best investigated CLP in cancer is YKL-40. Serum and plasma levels of YKL-40 correlate with poor prognosis in breast, lung, prostate, liver, bladder, colon and other types of cancers. In combination with other circulating factors YKL-40 can be used as a predictive biomarker of cancer outcome. In experimental models YKL-40 supports tumor initiation through binding to RAGE, and is able to induce cancer cell proliferation via ERK1/2-MAPK pathway. YKL-40 supports tumor angiogenesis by interaction with syndecan-1 on endothelial cells and metastatic spread by stimulating production of pro-inflammatory and pro-invasive factors MMP9, CCL2 and CXCL2. CLPs induce production of pro- and anti-inflammatory cytokines and chemokines, and are potential modulators of inflammatory tumor microenvironment. Targeting YKL-40 using neutralizing antibodies exerts anti-cancer effect in preclinical animal models. Multifunctional role of CLPs in regulation of inflammation and intratumoral processes makes them attractive candidates for tumor therapy and immunomodulation. In this review we comprehensively analyze recent data about expression pattern, and involvement of human CLPs in cancer.