Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions

Life Sci. 2003 Aug 1;73(11):1427-36. doi: 10.1016/s0024-3205(03)00434-x.

Abstract

This study aims to investigate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in giant cell tumor of bone (GCT) and other osteolytic lesions in bone. By using semi-quantitative RT-PCR, we showed that three major isoforms of VEGF (121, 165 and 189) were expressed in GCTs, with isoform 121 being the most abundant. The expression levels of VEGF and MMP-9 mRNA were significantly higher in advanced GCTs (stage II/III) than in stage I GCTs. We further elucidated the cellular localization of VEGF and MMP-9 gene transcripts in GCT and other osteolytic lesions using an in situ hybridization assay. The results showed that stromal tumor cells and osteoclast-like giant cells of GCT, fibrous stromal cells in anuerysmal bone cysts and fibrous dysplasia, and Langerhans-type giant cells as well as histocytes in eosinophillic granuloma, were all strongly positive for VEGF and MMP-9 mRNA expression. In a prospective study, we performed VEGF and MMP-9 immuno-staining on paraffin sections of pathological tissues harvested from 48 patients (14 GCT, 10 anuerysmal bone cysts, 10 eosinophillic granuloma, 4 fibrous dysplasia, 2 simple bone cyst, 2 osteomyelitis and 6 patients with fractured femoral head as control). The results showed that the differences in VEGF and MMP-9 expression between Stage I and other advanced Stages (II, III and recurrent) were highly significant (p<0.001), with advanced stages showing a higher mean expression. The difference between recurrent and Stage II and III lesions, was also statistically significant (p=0.03 for VEGF, and p=0.01 for MMP-9 expression), with recurrent lesions showing a higher mean expression of both VEGF and MMP-9. In conclusion, VEGF and MMP-9 expression in osteolytic lesions of bone co-relates well with the extent of bone destruction and local recurrence. Their expression may therefore provide some prognostic indication of the possible aggressive behavior of the underlying pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Cysts / metabolism
  • Bone Cysts, Aneurysmal / metabolism
  • Bone Neoplasms / chemistry*
  • Bone Neoplasms / pathology
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / genetics*
  • Fibrous Dysplasia of Bone / metabolism
  • Gene Expression
  • Giant Cell Tumor of Bone / chemistry*
  • Giant Cell Tumor of Bone / pathology
  • Granuloma / metabolism
  • Histiocytes / chemistry
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lymphokines / analysis
  • Lymphokines / genetics*
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / genetics*
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Osteoclasts / chemistry
  • Osteolysis / metabolism*
  • Osteomyelitis / metabolism
  • Prospective Studies
  • Protein Isoforms / genetics
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / chemistry
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Protein Isoforms
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 9