Lysyl oxidase and enhancement of cell proliferation and angiogenesis in oral squamous cell carcinoma

Head Neck. 2013 Feb;35(2):250-6. doi: 10.1002/hed.22959. Epub 2012 Feb 24.

Abstract

Background: Lysyl oxidase (LOX) is a copper-dependent enzyme that cross-links collagen and elastin in the extracellular matrix. LOX overexpressed in various tumors. The manner in which LOX affects tumor growth remains controversial.

Methods: Chemical treatment and gene transfection were used to induce LOX overexpression or inhibition in cell lines SAS and SVEC4-10. LOX mRNA, protein, and activity were confirmed before tube formation assay and tumorigenesis. The microvessels in the tumor section were detected by immunostaining CD31-positive endothelial cells.

Results: LOX overexpression and copper induction of LOX activity increased SVEC4-10 tube formation. LOX silencing and β-aminopropionitrile inhibition of LOX activity had opposite effects. LOX overexpression increased proliferation and proliferating cell nuclear antigen expression. High LOX expression clones increased tumor size in a tumorigenesis model. The microvascular numbers were higher in LOX overexpression tumors than in control tumors.

Conclusion: LOX can induce cell proliferation and angiogenesis in oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Copper / pharmacology*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Immunohistochemistry
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / genetics*
  • Protein-Lysine 6-Oxidase / genetics*
  • Protein-Lysine 6-Oxidase / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • Copper
  • cuprous chloride
  • Protein-Lysine 6-Oxidase