YKL-40, a secreted glycoprotein, promotes tumor angiogenesis

Oncogene. 2009 Dec 17;28(50):4456-68. doi: 10.1038/onc.2009.292. Epub 2009 Sep 21.


Tumor angiogenesis is of paramount importance in solid tumor development. Elevated serum levels of YKL-40, which is a secreted heparin-binding glycoprotein, have been associated with a worse prognosis from various advanced human cancers. Yet the role of YKL-40 activity in these cancers is still missing. In this study, we showed that ectopic expression of YKL-40 in MDA-MB-231 breast cancer cells and in HCT-116 colon cancer cells led to larger tumor formation with an extensive angiogenic phenotype than did control cancer cells in mice. Affinity-purified recombinant YKL-40 protein promoted vascular endothelial cell angiogenesis in vitro, the effects of which are similar to the activities observed using MDA-MB-231 and HCT-116 cell-conditioned medium after transfection with YKL-40. Furthermore, YKL-40 was found to induce coordination of membrane-bound receptor syndecan-1 and integrin alpha(v)beta(3) and to activate an intracellular signaling cascade, including focal adhesion kinase and mitogen-activated protein kinase extracellular signal-related kinase1/2 in endothelial cells. Moreover, blockade of YKL-40 using small-interfering RNA gene knockdown suppressed tumor angiogenesis in vitro and in vivo. Immunohistochemical analysis of human breast cancer showed a correlation between YKL-40 expression and blood vessel density. These findings provide novel insights into angiogenic activities and molecular mechanisms of YKL-40 in cancer development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipokines
  • Animals
  • Biglycan
  • Cell Line, Tumor
  • Cell Proliferation
  • Chitinase-3-Like Protein 1
  • Endothelial Cells / physiology
  • Extracellular Matrix Proteins / physiology
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Focal Adhesion Protein-Tyrosine Kinases / physiology
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / physiology*
  • Humans
  • Integrin alphaVbeta3 / physiology
  • Lectins / antagonists & inhibitors
  • Lectins / physiology*
  • Mice
  • Mice, SCID
  • Neoplasms / blood supply*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / etiology*
  • Proteoglycans / physiology


  • Adipokines
  • BGN protein, human
  • Bgn protein, mouse
  • Biglycan
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Integrin alphaVbeta3
  • Lectins
  • Proteoglycans
  • Focal Adhesion Protein-Tyrosine Kinases
  • Extracellular Signal-Regulated MAP Kinases