Title
Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer
Author
Kubben, F.J.G.M.
Sier, C.F.M.
Hawinkels, L.J.A.C.
Tschesche, H.
van Duijn, W.
Zuidwijk, K.
van der Reijden, J.J.
Hanemaaijer, R.
Griffioen, G.
Lamers, C.B.H.W.
Verspaget, H.W.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
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.
Subject
Biology
Biomedical Research
Activity assay
Cancer
Metalloproteinase
Prognosis
gelatinase B
lipocalin
matrix metalloproteinase inhibitor
tissue inhibitor of metalloproteinase 1
adult
aged
article
autolysis
cancer survival
disease classification
enzyme activity
enzyme degradation
epithelium cell
female
human
human tissue
immunohistochemistry
major clinical study
male
multivariate analysis
priority journal
protein function
stomach cancer
tumor
univariate analysis
world health organization
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http://resolver.tudelft.nl/uuid:c405229a-6899-4dc8-83a4-96c1c69cd431
DOI
https://doi.org/10.1016/j.ejca.2007.05.013
TNO identifier
240104
ISSN
0959-8049
Source
European Journal of Cancer, 43 (12), 1869-1876
Document type
article