Regulation of YKL‐40 expression during genotoxic or microenvironmental stress in human glioblastoma cells

YKL‐40 is a 40 kDa secreted glycoprotein belonging to the family of ‘mammalian chitinase‐like proteins’, but without chitinase activity. YKL‐40 has a proliferative effect on fibroblasts, chondrocytes and synoviocytes, and chemotactic effect on endothelium and vascular smooth muscle cells. Elevated YKL‐40 levels are found in serum of patients with diseases characterized by inflammation, fibrosis and tissue remodeling. Several studies have reported that high serum YKL‐40 levels in patients with cancer are associated with poor prognosis. YKL‐40 expression is strongly elevated in serum and biopsy material from glioblastomas patients. We investigated the expression of YKL‐40 in three human malignant glioma cell lines exposed to different types of stress. Whereas a polymerase chain reaction transcript was detectable in all three cell lines, only U87 produced measurable amounts of YKL‐40 protein. In U87, hypoxia and ionizing radiation induced a significant increase in YKL‐40 after 24–48 h. The hypoxic induction of YKL‐40 was independent of HIF1. Etoposide, ceramide, serum depletion and confluence all led to elevated YKL‐40. Inhibition of p53 augmented the YKL‐40 expression indicating that YKL‐40 is attenuated by p53. In contrast, both basic fibroblast growth factor and tumor necrosing factor‐α repressed YKL‐40. These are the first data on regulation of YKL‐40 in cancer cells. Diverse types of stress resulted in YKL‐40 elevation, which strongly supports an involvement of YKL‐40 in the malignant phenotype as a cellular survival factor in an adverse microenvironment. (Cancer Sci 2005; 96: 183–190)