Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer
article
Recently, complexes of matrix metalloproteinase matrix metalloproteinase-9 (MMP-9) with lipocalin-2 (neutrophil gelatinase-associated lipocalin) were found in the urine obtained from breast cancer patients, while these were completely absent in that obtained from healthy controls. In vitro data suggested a possible role for lipocalin-2 in the protection of MMP-9 against autolysis. To establish this effect in vivo, we determined the presence of MMP-9, lipocalin-2 and their complex in tumour tissue from 81 gastric cancer patients. The effect of the presence of the individual parameters, the complexes, and the inhibitors TIMP-1 and TIMP-2 on MMP-9 activity was evaluated with a bioactivity assay. Immuno-histochemical (double) staining identified epithelial cells as the most likely cellular source. Finally, evaluation of all these parameters with clinico-pathological scores revealed that tumour MMP-9/lipocalin-2 complexes were significantly related with the classifications of Laurén and WHO, and highly associated with worse survival in Cox's univariate (HR 2.087, P = 0.006) and multivariate analyses (HR 2.095, P = 0.025). © 2007 Elsevier Ltd. All rights reserved.
Topics
Biomedical ResearchActivity assayCancerMetalloproteinasePrognosisGelatinase BLipocalinMatrix metalloproteinase inhibitorTissue inhibitor of metalloproteinase 1AdultAgedAutolysisCancer survivalDisease classificationEnzyme activityEnzyme degradationEpithelium cellFemaleHumanHuman tissueImmunohistochemistryMajor clinical studyMaleMultivariate analysisPriority journalProtein functionStomach cancerTumorUnivariate analysisWorld health organization
TNO Identifier
240104
ISSN
09598049
Source
European Journal of Cancer, 43(12), pp. 1869-1876.
Pages
1869-1876
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