Expression of MMP-13 is associated with invasion and metastasis of papillary thyroid carcinoma

Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):427-35.

Abstract

Background: Collagenase-3 (MMP-13), a matrix metalloproteinase, is a recently identified member of the matrix metalloproteinases (MMPs) with broad substrate specificity, and a potential role in tumor metastasis and invasion has been proposed. Collagenase-3 expression has been reported in many carcinomas. However, the presence and possible implication of MMP-13 in the progression of papillary thyroid carcinomas are unknown.

Materials and methods: In the present study, we examined MMP-13 gene expression in 208 papillary thyroid carcinomas who underwent surgery without preoperative treatment and 100 matched samples of adjacent normal thyroid tissue (Paraffin-embedded tissue samples) by immunohistochemistry analysis. In vitro and in vivo studies were done in order to investigate the effect of MMP-13 overexpression or silencing on cancer cells invasion and metastasis.

Results: We found MMP-13 expression was significantly increased in the tumours from local regional lymph node metastases patients. The MMP-13 was stained more intensely in invading fronts than in central portions of local regional lymph node. No MMP-13 staining was observed in matched samples of adjacent normal thyroid tissue. MMP-13 expression was significantly related with TNM and recurrent disease, no relation was found with age extent of tumour and size of tumour. Studies with cell and mice models indicated that overexpression of MMP-13 increased cell migration and promoted metastasis, and MMP-13 sliencing decreased cell migration.

Conclusions: The data suggest that MMP-13 is associated with thyroid tumour invasion and metastasis and it may be a potential target for therapeutic intervention.

MeSH terms

  • Adult
  • Animals
  • Blotting, Western
  • Carcinoma / enzymology
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma, Papillary
  • Case-Control Studies
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression
  • Female
  • Gene Expression*
  • Gene Silencing
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Matrix Metalloproteinase 13 / genetics*
  • Mice
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Gland / enzymology*
  • Thyroid Neoplasms / enzymology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism

Substances

  • RNA, Small Interfering
  • MMP13 protein, human
  • Matrix Metalloproteinase 13