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. 1998 Dec;43(6):791–797. doi: 10.1136/gut.43.6.791

Matrix metalloproteinases and their inhibitors in gastric cancer

G Murray 1, M Duncan 1, E Arbuckle 1, W Melvin 1, J Fothergill 1
PMCID: PMC1727341  PMID: 9824606

Abstract

Background—The matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are strongly implicated in tumour invasion and metastasis. 
Aims—To investigate the presence of individual MMPs and TIMPs in gastric cancer. 
Methods—The presence of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 was identified in a group of gastric cancers (n=74) by immunohistochemistry using monoclonal antibodies. These antibodies were effective on formalin fixed, paraffin wax embedded sections. 
Results—A large proportion (94%) of gastric cancers contained MMP-2; MMP-1 and MMP-9 were also detected in 73% and 70% of tumours respectively. MMP-3 was only present in 27% of tumours. MMP-1 and MMP-9 were found predominantly in intestinal type tumours. TIMP-1 and TIMP-2 were identified in 41% and 57% of tumours respectively. Immunoreactivity for individual MMPs or TIMPs was not identified in normal stomach. 
Conclusions—This study shows the presence of matrix metalloproteinases, particularly MMP-2, and TIMPs in stomach cancer. Antibodies which are effective in formalin fixed, paraffin wax embedded sections are useful for the identification of MMPs and TIMPs in diagnostic specimens. 



Keywords: immunohistochemistry; matrix metalloproteinase; neoplasm; stomach

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Figure 1 .

Figure 1

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Immunoblot showing the specificity of the MMP-1, MMP-2, MMP-3, and MMP-9 antibodies. The membrane was immunostained with MMP-1 (A), MMP-2 (B), MMP-3 (C), and MMP-9 antibody (D). Lane 1, MMP-1; lane 2, MMP-3; lane 3, MMP-2; lane 4, MMP-9. Molecular weight markers are shown on the right in kDa. 


Figure 2 .

Figure 2

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Immunoblots showing the reaction of the MMP-1, MMP-2, MMP-3, and MMP-9 monoclonal antibodies with the proenzyme and activated forms of the corresponding MMPs. The membrane was immunostained with MMP-1 (A), MMP-2 (B), MMP-3 (C), and MMP-9 antibody (D). Lane 1 contained the proenzyme and lane 2 the activated form of the MMP corresponding to the monoclonal antibody used for the immunostaining. Molecular weight markers are shown on the right in kDa. 


Figure 3 .

Figure 3

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Immunohistochemical localisation of: (A) MMP-1; (B) MMP-2; (C) MMP-3; (D) MMP-9 in gastric cancers of intestinal type; and (E) MMP-1 in normal gastric epithelium (similar results were obtained with antibodies to the other MMPs). Strong immunoreactivity for each MMP is present in tumour cells (arrows) and is not present in normal gastric epithelium (original magnification ×120).


Figure 4 .

Figure 4

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Immunoblot showing the specificity of the TIMP-1 and TIMP-2 antibodies. Section A was immunostained with TIMP-1 antibody and section B with TIMP-2 antibody. Lane 1, TIMP-1; lane 2, TIMP-2. Molecular weight markers are shown on the right in kDa. 


Figure 5 .

Figure 5

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Immunohistochemical localisation of (A) TIMP-1 and (B) TIMP-2 in gastric cancers of intestinal type. TIMP-1 and TIMP-2 immunoreactivity is present in tumour cells (arrows). Immunostaining for TIMP-1 is also present in macrophages (arrowhead) and immunostaining for TIMP-2 is also present in fibroblasts (arrowhead) (original magnification ×120). 


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