Expression of αvβ6 integrin and collagen fibre in oral squamous cell carcinoma: association with clinical outcomes and prognostic implications

J Oral Pathol Med. 2013 Aug;42(7):547-56. doi: 10.1111/jop.12044. Epub 2013 Jan 18.

Abstract

Background: This study aims to investigate the expression and significance of the αvβ6 integrin, collagen fibres and matrix metalloproteinases (MMP)-3 in oral squamous cell carcinoma (OSCC) and to analyse the possible regulatory relationships between αvβ6, collagen fibres and MMP-3.

Materials and methods: A series of 80 patients (mean age 56.4 years) diagnosed with OSCC were enrolled. Associations between αvβ6, MMP-3, collagen fibre expression levels and clinicopathological parameters were evaluated using the Fisher exact test. Survival analysis was performed with Kaplan-Meier curves. Spearman rank correlation was used to analyse interactions between αvβ6, MMP-3 and collagen fibres.

Results: αvβ6 and MMP-3 were strongly expressed in human OSCC, especially at the peripheral borders of invasive tumour islands, and collagen fibres were generally disrupted and degraded in the same areas. The expression intensity of αvβ6 was associated with the differentiation state of cells. β6 mRNA was expressed in almost all cancer cells. In carcinomas, αvβ6 and MMP-3 expression were correlated with the distribution of collagen fibres.

Conclusions: Tumour cells highly expressing αvβ6 have a strong capability for invasion and migration, due to concomitant protease production and the destruction and remodelling of collagen fibres. Increased αvβ6 integrin and MMP-3 expression and collagen fibre changes in human OSCCs are related to unfavourable clinical prognostic factors and decreased survival.

Keywords: MMP-3; collagen fibre; oral squamous cell carcinoma; prognosis; αvβ6 integrin.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / analysis*
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / secondary
  • Cell Differentiation / physiology
  • Cell Movement / physiology
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Collagen / analysis*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin beta Chains / analysis
  • Integrins / analysis*
  • Lymphatic Metastasis / pathology
  • Male
  • Matrix Metalloproteinase 3 / analysis*
  • Middle Aged
  • Mouth Neoplasms / pathology*
  • Neoadjuvant Therapy
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Tumor Microenvironment / physiology

Substances

  • Antigens, Neoplasm
  • Integrin beta Chains
  • Integrins
  • integrin alphavbeta6
  • integrin beta6
  • Collagen
  • MMP3 protein, human
  • Matrix Metalloproteinase 3