Abstract
It is now recognised that epithelial-stromal interactions are important in a wide range of disease processes including neoplasia and inflammation. Metalloproteinases are central to matrix degradation and remodelling, which are key events in tumour invasion and metastasis and may also be involved in tissue changes occurring in chronic inflammation. Immunohistochemistry was performed on sections from 50 patients with pancreatic cancer (n = 27), ampullary cancer (n = 12), low bile duct cancer (n = 3), neuroendocrine tumours (n = 3) and chronic pancreatitis (n = 5), using antibodies raised against collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of metalloproteinase (TIMP1) and developed using the avidin-biotin complex method. Abundance of MMP2, MMP3 and TIMP1 was greater in pancreatic and ampullary cancer than any other pathology and immunoreactivity in the malignant epithelial cells in pancreatic and ampullary cancer was greater than in the stromal tissues (in pancreatic cancer: MMP2 100% vs 37%, MMP3 93% vs 15%, TIMP1 93% vs 4%, P < 0.0001). There were strong correlations between the immunoreactivity of the two antibodies for MMP2 (P < 0.0001), between MMP2 and TIMP1 (P < 0.0001) and between MMP3 and TIMP1 (P < 0.0001). The immunoreactivity for TIMP1 in pancreatic and ampullary cancers with lymph node metastases was significantly less compared with those cases without lymph node metastases (P < 0.02) and there was an association between increased immunoreactivity for MMP2 and the degree of tumour differentiation (P < 0.01). The results implicate MMP2, MMP3 and TIMP1 in the invasive phenotype of pancreatic and ampullary cancer.
Highlights
This study reports the localisation of the protein products for MMP2, MMP3 and tissue inhibitor of metalloproteinase (TIMPI) in these different types of cancer using immunohistochemistry
Four monoclonal murine antibodies were used that are specific to the 72 kDa type IV collagenase (MMP2, antibodies GL22 and GL8), stromelysin 1 (MMP3, antibody Mac78) and the tissue inhibitor of the metalloproteinases (TIMPI, antibody Macl5)
Immunoreactivities for MMP2, MMP3 and TIMPI were greatest in adenocarcinomas of pancreas and ampulla compared with those in the other pathologies
Summary
Four monoclonal murine antibodies were used that are specific to the 72 kDa type IV collagenase (MMP2, antibodies GL22 and GL8), stromelysin 1 (MMP3, antibody Mac78) and the tissue inhibitor of the metalloproteinases (TIMPI, antibody Macl). Four monoclonal murine antibodies were used that are specific to the 72 kDa type IV collagenase (MMP2, antibodies GL22 and GL8), stromelysin 1 (MMP3, antibody Mac78) and the tissue inhibitor of the metalloproteinases (TIMPI, antibody Macl5) These antibodies were raised against recombinant enzymes and subsequently characterised by Western blotting. They were compared with all members of the MMP/TIMP family to confirm specificity and absorption controls with recombinant enzymes performed.
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