The non glycanated endocan polypeptide slows tumor growth by inducing stromal inflammatory reaction

Oncotarget. 2015 Feb 20;6(5):2725-35. doi: 10.18632/oncotarget.2614.


Endocan expression is increasingly studied in various human cancers. Experimental evidence showed that human endocan, through its glycan chain, is implicated in various processes of tumor growth. We functionally characterize mouse endocan which is also a chondroitin sulfate proteoglycan but much less glycanated than human endocan. Distant domains from the O-glycanation site, located within exons 1 and 2 determine the glycanation pattern of endocan. In opposite to the human homologue, overexpression of mouse endocan in HT-29 cells delayed the tumor appearance and reduced the tumor growth rate. This tumor growth inhibition is supported by non glycanated form of mouse endocan. Non glycanated human endocan overexpressed in HT-29, A549 or K1000 cells also exhibited an anti-tumor effect. Moreover, systemic delivery of non glycanated human endocan also results in HT-29 tumor growth delay. In vitro, endocan polypeptide did not affect HT-29 cell proliferation, nor cell viability. In tumor tissue sections, a stromal inflammatory reaction was observed only in tumors overexpressing endocan polypeptide, and depletion of CD122+ cells was able to delete partially the anti-tumor effect of endocan polypeptide. These results reveal a novel pathway for endocan in the control of tumor growth, which involves inflammatory cells of the innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy
  • Cricetulus
  • Genetic Therapy
  • Glycosylation
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Immunity, Innate
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Interleukin-2 Receptor beta Subunit / metabolism
  • Male
  • Mice
  • Mice, SCID
  • NIH 3T3 Cells
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Protein Structure, Tertiary
  • Proteoglycans / genetics
  • Proteoglycans / metabolism*
  • Signal Transduction
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Time Factors
  • Transfection
  • Xenograft Model Antitumor Assays


  • ESM1 protein, human
  • Interleukin-2 Receptor beta Subunit
  • Neoplasm Proteins
  • Proteoglycans
  • endothelial cell-specific molecule-1, mouse