Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer

PLoS One. 2016 Sep 9;11(9):e0162189. doi: 10.1371/journal.pone.0162189. eCollection 2016.

Abstract

Background: Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth.

Methods: Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA.

Results: Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected.

Conclusions: To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.

MeSH terms

  • Chitinase-3-Like Protein 1 / blood*
  • Colonic Neoplasms / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Inflammation / blood
  • Linear Models
  • Male
  • Middle Aged
  • Obesity / blood
  • Osteopontin / blood*
  • Tenascin / blood*

Substances

  • Chitinase-3-Like Protein 1
  • Extracellular Matrix Proteins
  • Tenascin
  • Osteopontin

Grants and funding

This work was supported by Fondo de Investigación Sanitaria-FEDER, Instituto de Salud Carlos III (ISCIII) (PI12/00515, PI13/00460 and PI14/00950), by the Department of Health (48/2011 and 58/2011) of the Gobierno de Navarra of Spain, by Fundación Caja Navarra (20-2014) and by the ISCIII, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, CIBEROBN, Spain.