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Role of matrix metalloproteinase (MMP) 2 and MMP-9 in soft tissue sarcoma.

Yang HK, Jeong KC, Kim YK, Jung ST - Clin Orthop Surg (2014)

Bottom Line: By Western blot analysis, the expression levels of MMP-2, TIMP-1, and TIMP-2 were higher in the metastatic group (p < 0.05), but MMP-9 showed only a slight increase in the metastatic group compared with 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), but the expression of the pro- and active forms of MMP-9 showed a slight decrease in the metastatic group (p > 0.05).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Chonnam National University Medical School, Gwangju, Korea.

ABSTRACT

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) by RT-PCR. By Western blot analysis, the expression levels of MMP-2, TIMP-1, and TIMP-2 were higher in the metastatic group (p < 0.05), but MMP-9 showed only a slight increase in the metastatic group compared with 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), but the expression of the pro- and active forms of MMP-9 showed a slight decrease 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.

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Immunohistochemical staining findings for matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitors of metalloproteinase (TIMP) 1, and TIMP-2 in the non-metastatic malignant fibrous histiocytoma (MFH) and metastatic MFH cells. MMP-2 and MMP-9 were weakly expressed in non-metastatic MFH cells (A, C), but predominantly expressed in metastatic MFH cells with diffuse, strong intensities (B, D). TIMP-1 and TIMP-2 showed negative expressions in non-metastatic MFH cells (E, G) and focal strong expression in metastatic MFH cells (F, H) (A-H, ×200). (A) MMP-2 in non-metastatic MFH. (B) MMP-2 in metastatic MFH. (C) MMP-9 in non-metastatic MFH. (D) MMP-9 in metastatic MFH. (E) TIMP-1 in non-metastatic MFH. (F) TIMP-1 in metastatic MFH. (G) TIMP-2 in non-metastatic MFH. (H) TIMP-2 in metastatic MFH.
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Figure 1: Immunohistochemical staining findings for matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitors of metalloproteinase (TIMP) 1, and TIMP-2 in the non-metastatic malignant fibrous histiocytoma (MFH) and metastatic MFH cells. MMP-2 and MMP-9 were weakly expressed in non-metastatic MFH cells (A, C), but predominantly expressed in metastatic MFH cells with diffuse, strong intensities (B, D). TIMP-1 and TIMP-2 showed negative expressions in non-metastatic MFH cells (E, G) and focal strong expression in metastatic MFH cells (F, H) (A-H, ×200). (A) MMP-2 in non-metastatic MFH. (B) MMP-2 in metastatic MFH. (C) MMP-9 in non-metastatic MFH. (D) MMP-9 in metastatic MFH. (E) TIMP-1 in non-metastatic MFH. (F) TIMP-1 in metastatic MFH. (G) TIMP-2 in non-metastatic MFH. (H) TIMP-2 in metastatic MFH.

Mentions: Immunohistochemical staining was done for MMP-2, MMP-9, TIMP-1, and TIMP-2 (Fig. 1). For MMP-2 in the non-metastatic group, 10 cases showed no expression, nine mild expression, and one moderate expression. The expression rate of MMP-2 in the non-metastatic MFH group was 50% (10 cases). The metastatic group showed four with mild expression, three with moderate expression, and three with diffuse expression. The expression rate of MMP-2 in the metastatic group was 100% (10 cases; p < 0.05). For MMP-9 in the non-metastatic group, six showed no expression, eight mild expression, five moderate expression, and one diffuse expression. The expression rate of MMP-9 in the non-metastatic group was 70% (14 cases). The metastatic group showed two cases of mild expression, one moderate expression, and seven diffuse expression (p < 0.05) (Table 3). The expression rate of MMP-9 in the metastatic group was 100% (10 cases; p < 0.05). The expression rates of TIMP-1 and TIMP-2 are shown in Table 4.


Role of matrix metalloproteinase (MMP) 2 and MMP-9 in soft tissue sarcoma.

Yang HK, Jeong KC, Kim YK, Jung ST - Clin Orthop Surg (2014)

Immunohistochemical staining findings for matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitors of metalloproteinase (TIMP) 1, and TIMP-2 in the non-metastatic malignant fibrous histiocytoma (MFH) and metastatic MFH cells. MMP-2 and MMP-9 were weakly expressed in non-metastatic MFH cells (A, C), but predominantly expressed in metastatic MFH cells with diffuse, strong intensities (B, D). TIMP-1 and TIMP-2 showed negative expressions in non-metastatic MFH cells (E, G) and focal strong expression in metastatic MFH cells (F, H) (A-H, ×200). (A) MMP-2 in non-metastatic MFH. (B) MMP-2 in metastatic MFH. (C) MMP-9 in non-metastatic MFH. (D) MMP-9 in metastatic MFH. (E) TIMP-1 in non-metastatic MFH. (F) TIMP-1 in metastatic MFH. (G) TIMP-2 in non-metastatic MFH. (H) TIMP-2 in metastatic MFH.
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Figure 1: Immunohistochemical staining findings for matrix metalloproteinase (MMP) 2, MMP-9, tissue inhibitors of metalloproteinase (TIMP) 1, and TIMP-2 in the non-metastatic malignant fibrous histiocytoma (MFH) and metastatic MFH cells. MMP-2 and MMP-9 were weakly expressed in non-metastatic MFH cells (A, C), but predominantly expressed in metastatic MFH cells with diffuse, strong intensities (B, D). TIMP-1 and TIMP-2 showed negative expressions in non-metastatic MFH cells (E, G) and focal strong expression in metastatic MFH cells (F, H) (A-H, ×200). (A) MMP-2 in non-metastatic MFH. (B) MMP-2 in metastatic MFH. (C) MMP-9 in non-metastatic MFH. (D) MMP-9 in metastatic MFH. (E) TIMP-1 in non-metastatic MFH. (F) TIMP-1 in metastatic MFH. (G) TIMP-2 in non-metastatic MFH. (H) TIMP-2 in metastatic MFH.
Mentions: Immunohistochemical staining was done for MMP-2, MMP-9, TIMP-1, and TIMP-2 (Fig. 1). For MMP-2 in the non-metastatic group, 10 cases showed no expression, nine mild expression, and one moderate expression. The expression rate of MMP-2 in the non-metastatic MFH group was 50% (10 cases). The metastatic group showed four with mild expression, three with moderate expression, and three with diffuse expression. The expression rate of MMP-2 in the metastatic group was 100% (10 cases; p < 0.05). For MMP-9 in the non-metastatic group, six showed no expression, eight mild expression, five moderate expression, and one diffuse expression. The expression rate of MMP-9 in the non-metastatic group was 70% (14 cases). The metastatic group showed two cases of mild expression, one moderate expression, and seven diffuse expression (p < 0.05) (Table 3). The expression rate of MMP-9 in the metastatic group was 100% (10 cases; p < 0.05). The expression rates of TIMP-1 and TIMP-2 are shown in Table 4.

Bottom Line: By Western blot analysis, the expression levels of MMP-2, TIMP-1, and TIMP-2 were higher in the metastatic group (p < 0.05), but MMP-9 showed only a slight increase in the metastatic group compared with 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), but the expression of the pro- and active forms of MMP-9 showed a slight decrease in the metastatic group (p > 0.05).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Chonnam National University Medical School, Gwangju, Korea.

ABSTRACT

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) by RT-PCR. By Western blot analysis, the expression levels of MMP-2, TIMP-1, and TIMP-2 were higher in the metastatic group (p < 0.05), but MMP-9 showed only a slight increase in the metastatic group compared with 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), but the expression of the pro- and active forms of MMP-9 showed a slight decrease 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.

Show MeSH
Related in: MedlinePlus