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

Cancer Sci. 2005 Mar;96(3):183-90. doi: 10.1111/j.1349-7006.2005.00026.x.


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-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Cell Hypoxia*
  • Cell Survival
  • Chitinase-3-Like Protein 1
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics*
  • Humans
  • Lectins
  • Oxidative Stress*
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Lectins