Pleiotrophin is a potential colorectal cancer prognostic factor that promotes VEGF expression and induces angiogenesis in colorectal cancer

Int J Colorectal Dis. 2012 Mar;27(3):287-98. doi: 10.1007/s00384-011-1344-z. Epub 2011 Nov 9.


Purpose: Pleiotrophin (PTN) is an important developmental secretory cytokine expressed in many types of cancer and involved in angiogenesis and tumor growth; however, the significance of PTN expression in colorectal cancer (CRC) has not been established.

Methods: Immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect PTN expression in CRC patients. The relationship between PTN expression and clinicopathological characteristics and survival time was statistically analyzed, and the relationship between PTN and vascular endothelial growth factor (VEGF) in tumor angiogenesis was further analyzed.

Results: Of CRC tissues, 74.70% (62/83) stained positive, with a strong positive ratio of 60.24% (50/83). The expression of PTN in CRC tissues was much higher than in normal colorectal tissues. PTN serum levels in CRC patients (mean = 254.59 ± 261.76 pg/ml) were significantly higher than those of normal volunteers (mean = 115.23 ± 79.53 pg/ml; p < 0.001). PTN expression was related to CRC differentiation and TNM staging. High level of PTN is a predictor of a poor prognosis and high expression of PTN is accompanied by high expression of VEGF in CRC patients. Investigation of the relationship between PTN and VEGF revealed that PTN, through the PTN/RPTPβ/ζ signaling pathway, increased tyrosine phosphorylation of β-catenin, leading to an increase in VEGF.

Conclusions: Our study identifies PTN as an essential growth factor for CRC. PTN promotes VEGF expression and cooperates with VEGF in promoting CRC angiogenesis. PTN could serve as a prognostic factor for this cancer. Considering that PTN shows very limited expression in normal tissue, it may represent an attractive new target for CRC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Caco-2 Cells
  • Carrier Proteins / blood
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Child
  • Colon / metabolism
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Cytokines / blood
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism
  • Phosphorylation / drug effects
  • Rectal Neoplasms / blood supply
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology
  • Rectum / metabolism
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*
  • Young Adult
  • beta Catenin / drug effects
  • beta Catenin / metabolism


  • Carrier Proteins
  • Cytokines
  • Vascular Endothelial Growth Factor A
  • beta Catenin
  • pleiotrophin