Role of Matrix Metalloproteinase (MMP) 2 and MMP-9 in Soft Tissue Sarcoma

BACKGROUND: We investigated the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in malignant fibrous histiocytoma (MFH), and determined whether these could be useful as prognostic factors. METHODS: Among patients treated from 1993 to 2007, 30 cases of MFH were evaluated. Immunohistochemical staining was performed for MMP-2, MMP-9, TIMP-1, and TIMP-2 using paraffin wax-embedded blocks of MFH tissues. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot and zymography were performed using fresh tissues obtained from 17 of the 30 cases. The levels of MMP and TIMP expression were compared between the MFH and normal control groups, and between non-metastatic and metastatic MFH groups. RESULTS: Expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were higher in the MFH group than the control group by RT-PCR, Western blotting, and zymography. Immunohistochemical staining revealed that MMP-2 and MMP-9 protein expression was higher in the metastatic than in the non-metastatic group. The expression levels of MMP-2 and TIMP-1 were significantly higher in the metastatic than in the non-metastatic group (p 0.05). Finally, gelatin zymography analysis showed that the expression levels of the pro- and active forms of MMP-2 were significantly higher in the metastatic group (p 0.05). CONCLUSIONS: These results suggest that MMP-2, MMP-9, TIMP-1, and TIMP-2 may have important roles in the development and progression of MFH, and that the degree of expression of these metalloproteinases and their inhibitors, especially MMP-2, could be useful as prognostic factors related to metastasis in MFH.

Increased Expression of the TGF-beta Isoform and Changed Contents of Collagen in Tendon of Cerebral Palsy Patients / 대한정형외과학회잡지

PURPOSE: This study measured the expression level of the transforming growth factor-beta (TGF-beta ) isoform expression and the collagen composition within the Achilles tendon from cerebral palsy (CP) patients. MATERIALS AND METHODS: The Achilles tendons were obtained from 15 CP patients with spastic equinovarus. The presence of the TGF-beta isoform and the composition of the collagen were examined histologically, performing by immunohistochemical staining (IHS) and determining the mRNA expression level using a reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: IHS revealed the presence of TGF-beta 1 and TGF-beta 2 expression in 2/15 cases and 4/15 cases respectively, and weak TGF-beta 3 expression in 7/15 cases. The TGF-beta 1 and TGF-beta 2 expression levels were uniform in all 15 cases according to RT-PCR, while TGF-beta 3 expression was observed in 8 out of 15 cases. IHS and RT-PCR showed strong TGF-beta 3 expression in 6/7 non-ambulatory patients. An immature form of collagen, type III collagen, was observed more abundantly in the non-ambulatory patients. CONCLUSION: These results suggest that contracture in CP may induce changes in the type of collagen via growth factors such as TGF-beta .

The Expression and Significance of TGF-beta Isoforms in Herniated Lumbar Intervertebral Disc / 대한정형외과학회잡지

PURPOSE: This study was conducted to determine the cellular role of TGF-beta in HNP specimens using immunohistochemistry stain (IHS) and reverse transcriptase-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: Disc tissues including the nucleus pulposus were collected from 19 patients who underwent disc resection due to radiculopathy. After performing IHS and RT-PCR on the HNP tissues, the correlation between TGF-beta isoform expression and other factors was investigated. RESULTS: In terms of isoform expression according to HNP types, TGF-beta 1 and- 2 were expressed weakly in the protruded type, whereas TGF-beta 1, - 2, and- 3 were expressed evenly in the extruded and sequestrated types. No significant differences in histological grades and TGF-beta expressions were observed according to the patients' age, sex, degree of intervertebral disc degeneration, sensory and motor nerve involvement, or symptomatic duration. A higher level of TGF-beta expression could be seen on immunohistological staining according to the grade of HNP exposure, and higher expression was also noted according to mRNA level using RT-PCR compared with the extruded and sequestrated types. CONCLUSION: However, further studies on differences in TGF-beta isofrom expression to the degree of degeneration are required, TGF-beta participates in wound healing and repair processes after the development of disc tissue damage. A possible application of TGF-beta as a new method for the treatment of HNP is expected.

The Clinical Significance of VEGF and TGF-beta Expression in Osteosarcoma / 대한정형외과학회잡지

INTRODUCTION: The transforming growth factor-beta (TGF-beta ) is a multipotent glycoprotein that has been implicated in tumor development. The vascular endothelial growth factor (VEGF), which is an endothelial-specific mitogen that is overexpressed in various malignancies, is believed to be a potent regulator of angiogenesis. Osteosarcoma was examined to determine firstly, if VEGF and the TGF-beta isoform were overexpressed in this sarcoma, and secondly, if the degree of expression might represent a significant biologic predictor for disease-specific survival. MATERIALS AND METHODS: Selected paraffin-embedded tissues of surgical specimens from 25 patients of prechemotherapy case with osteosarcoma, who were treated between 1995 and 2001 were stained with rabbit polyclonal anti-VEGF and TGF-beta isoform antibodies. RESULTS: The majority of high-grade osteosarcomas in this study had a high intensity TGF-beta 2, - 3 and VEGF expression levels. The three in 5 patients who died of the disease had a high VEGF expression level. However VEGF expression was only independent predictor of overall survival. CONCLUSION: Further studies about TGF-beta and VEGF may provide useful information for understanding of pathophysiology of osteosarcoma.