IngentaConnect Regulation of YKL-40 expression during genotoxic or microenvironm...

Authors: Junker, Nanna¹; Johansen, Julia S.²; Hansen, Lasse T.¹; Lund, Eva L.¹; Kristjansen, Paul E.G.

Source: Cancer Science, Volume 96, Number 3, March 2005 , pp. 183-190(8)

Abstract:

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. (Cancer Sci 2005; 96: 183–190)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2005.00026.x

Affiliations: 1: Laboratory of Experimental Oncology, Department of Molecular Pathology, University of Copenhagen, 2: Department of Rheumatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

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