Up-regulation of the novel proinflammatory adipokines lipocalin-2, chitinase-3 like-1 and osteopontin as well as angiogenic-related factors in visceral adipose tissue of patients with colon cancer

J Nutr Biochem. 2011 Jul;22(7):634-41. doi: 10.1016/j.jnutbio.2010.04.015. Epub 2010 Oct 18.


Background: Obesity is widely recognised as an important risk factor for colorectal cancer (CC).

Aim: The study aimed to evaluate the effect of CC on circulating concentrations and gene expression levels of inflammatory and angiogenesis-related factors in human visceral adipose tissue (VAT).

Methods: VAT biopsies were obtained from 18 healthy individuals and 11 patients with CC. Real-time polymerase chain reactions were performed to quantify gene expression levels and zymographic analyses were used to determine the activity of matrix metalloproteinases (MMPs).

Results: Patients with CC exhibited increased mRNA expression levels of lipocalin-2 (P=.014), osteopontin (P=.027), tumor necrosis factor-α (TNF-α) (P=.016) and chitinase-3 like-1 (P=.006) compared to control subjects in VAT. Gene expression levels of hypoxia-inducible factor-1 α, vascular endothelial growth factor and MMP-2 were significantly higher (P<.05) in VAT of patients with CC. The expression of insulin-like growth factor I, insulin growth factor binding protein 3 and MMP-9 followed the same trend, although no significant differences were reached. The enzymatic activity of MMP-9 was increased (P<.001) in patients with CC. Furthermore, individuals with CC showed increased (P<.05) circulating concentrations of the inflammatory markers interleukin-6, tumour necrosis factor α and hepatocyte growth factor, whereas levels of the anti-inflammatory adipokine adiponectin were decreased (P<.01).

Conclusion: These findings represent the first observation that mRNA levels of the novel inflammatory factors lipocalin-2, chitinase-3 like-1 and osteopontin are increased in human VAT of subjects with CC. This observation together with the up-regulation of angiogenic factors suggests that adipokines secreted by VAT may be involved in the development of colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis*
  • Adipokines
  • Adult
  • Aged
  • Angiogenesis Inducing Agents
  • Chitinase-3-Like Protein 1
  • Chitinases / biosynthesis*
  • Colonic Neoplasms / metabolism*
  • Glycoproteins / biosynthesis*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Intra-Abdominal Fat / metabolism*
  • Lectins / biosynthesis*
  • Lipocalin-2
  • Lipocalins / biosynthesis*
  • Matrix Metalloproteinases / biosynthesis
  • Middle Aged
  • Osteopontin / biosynthesis*
  • Proto-Oncogene Proteins / biosynthesis*
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / biosynthesis


  • Acute-Phase Proteins
  • Adipokines
  • Angiogenesis Inducing Agents
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • LCN2 protein, human
  • Lectins
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Osteopontin
  • Chitinases
  • Matrix Metalloproteinases