Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas

Head Neck. 2006 Jan;28(1):31-9. doi: 10.1002/hed.20298.

Abstract

Background: Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness. This study investigates the expression status of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in head and neck squamous cell carcinomas (HNSCC).

Methods: Of 48 laryngeal squamous cell carcinoma (LSCC) biopsies and 10 HNSCC cell lines, mRNA was isolated, reversely transcribed, and subjected to polymerase chain reaction (PCR) amplifying MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, and TIMP-2. Silver nitrate-stained gel electrophoresis demonstrated MMP and TIMP expression status. Exemplary immunohistochemistry and zymography confirmed translation and enzyme activity.

Results: Densitometric analysis revealed MMP-2 expression and lymph node metastases to be positively and TIMP-1 and TIMP-2 to be negatively correlated with lymph node metastases. TIMP-2 expression and tumor size were negatively correlated. MMP-1, MMP-9, and MMP-10 expression were not correlated to metastasis formation or tumor size.

Conclusions: Our results suggest that MMP-2 expression enhances, whereas TIMP-1 and TIMP-2 both suppress, cancer spread in LSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Polymerase Chain Reaction
  • Sequence Analysis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • Matrix Metalloproteinase Inhibitors
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinases