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PMID: 8611434 Published · ppublish English Journal Article

Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease.

British journal of cancer ·Vol. 73 ·No. 8 ·1996-04-00 ·Pages 972-8

Bramhall SR, Stamp GW, Dunn J, Lemoine NR, Neoptolemos JP

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.

MeSH Terms
Ampulla of Vater Animals Common Bile Duct Neoplasms/chemistry Gelatinases/analysis,immunology Glycoproteins/analysis,immunology Humans Immunohistochemistry Matrix Metalloproteinase 2 Matrix Metalloproteinase 3 Metalloendopeptidases/analysis,immunology Mice Pancreatic Neoplasms/chemistry Tissue Inhibitor of Metalloproteinases
Chemicals
Glycoproteins Tissue Inhibitor of Metalloproteinases Gelatinases Metalloendopeptidases Matrix Metalloproteinase 3 Matrix Metalloproteinase 2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bramhall S R
Department of Surgery, City Hospital NHS Trust Birmingham, UK.
Stamp G W
Dunn J
Lemoine N R
Neoptolemos J P
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/bjc.1996.190
Published
1996-04-00
Pages
972-8
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2075817
Subset
IM
External Links
PubMed source DOI: 10.1038/bjc.1996.190 PMC Full Text View journal details
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