Human colorectal cancer progression correlates with LOX-induced ECM stiffening

Int J Biol Sci. 2017 Nov 1;13(11):1450-1457. doi: 10.7150/ijbs.21230. eCollection 2017.

Abstract

Some solid tumors are characterized by extracellular matrix (ECM) remodeling and stiffening, which is related to solid tumor progression and aggression. However, the relationship between ECM stiffness and colorectal cancer (CRC) remains unclear. In this study, we investigated the relevance of ECM stiffness to clinicopathologic features using human CRC tissue microarrays. The results demonstrate that the expression of ECM components in CRC tissues is closely correlated with CRC progression and poor prognosis, which indicates that ECM stiffness may be associated with CRC development. We further studied lysyl oxidase (LOX) expression in CRC tissue and demonstrated that LOX expression is closely correlated with CRC progression. Previous studies showed that P-selectin-mediated platelet accumulation in CRC tissue may up-regulate LOX expression. Our findings indicate that P-selectin-mediated platelet aggregation may up-regulate LOX expression and enhance the remodeling and stiffening of the tumor ECM, which may promote the progression of colorectal cancer. Therefore, LOX may be a potential effective therapeutic target to treat colorectal cancer.

Keywords: LOX; colorectal cancer.; tissue stiffness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Humans
  • Immunohistochemistry
  • P-Selectin / genetics
  • P-Selectin / metabolism
  • Protein-Lysine 6-Oxidase / genetics
  • Protein-Lysine 6-Oxidase / metabolism*
  • Tissue Array Analysis

Substances

  • Collagen Type I
  • P-Selectin
  • Protein-Lysine 6-Oxidase