Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Digestion. 2018;98(4):238-248. doi: 10.1159/000489558. Epub 2018 Jul 25.

Abstract

Background/aims: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining.

Methods: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members - LOXL1, LOXL3, and LOXL4 - were investigated by immunohistochemical studies. The effect of the transforming growth -factor β1 (TGFβ1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro.

Results: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFβ decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression.

Conclusion: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.

Keywords: Gastric cancer; Lysyl oxidase like 1; Lysyl oxidase like 3; Lysyl oxidase like 4; Transforming growth factor β1.

MeSH terms

  • Amino Acid Oxidoreductases / metabolism*
  • Carcinoma / genetics
  • Carcinoma / mortality
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Female
  • Gastric Mucosa / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Protein-Lysine 6-Oxidase
  • Recombinant Proteins / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Analysis
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Microenvironment

Substances

  • Recombinant Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human
  • LOXL3 protein, human
  • LOXL4 protein, human
  • Protein-Lysine 6-Oxidase