Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

Br J Cancer. 2014 Oct 14;111(8):1605-13. doi: 10.1038/bjc.2014.456. Epub 2014 Aug 19.

Abstract

Background: Endostatin, a fragment of collagen XVIII, is an endogenous angiogenesis inhibitor with anti-tumour functions. However, elevated circulating endostatin concentrations have been found in several human cancers including colorectal cancer (CRC).

Methods: Serum endostatin levels were measured by enzyme-linked immunoassay from a series of 143 patients with CRC and from 84 controls, and correlated with detailed clinicopathological features of CRC, serum leukocyte differential count and C-reactive protein (CRP) levels.

Results: Patients with CRC had higher serum endostatin levels than the controls (P=0.005), and high levels associated with age, tumour invasion through the muscularis propria and poor differentiation, but not with metastases. Endostatin levels showed a positive correlation with the markers of systemic inflammatory response and a negative correlation with the densities of tumour-infiltrating mast cells and dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in blood vessels and capillaries, and in the muscle layer of the bowel wall.

Conclusions: Elevated endostatin levels in CRC correlate with systemic inflammation and invasion through the muscularis propria. Increased endostatin level may be a result of invasion-related cleavage of collagen XVIII expressed in the bowel wall. The negative correlations between serum endostatin and intratumoural mast cells and immature dendritic cells may reflect angiogenesis inhibition by endostatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Collagen Type XVIII / metabolism
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / pathology
  • Endostatins / blood*
  • Female
  • Humans
  • Inflammation / blood*
  • Inflammation / complications
  • Male
  • Middle Aged
  • Neoplasm Invasiveness*

Substances

  • Biomarkers, Tumor
  • Collagen Type XVIII
  • Endostatins