Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer

Kubben FJGM, Sier CFM, Hawinkels LJAC, Tschesche H, van Duijn W, Zuidwijk K, van der Reijden JJ, Hanemaaijer R, Griffioen G, Lamers CBHW, Verspaget HW (2007)
EUROPEAN JOURNAL OF CANCER 43(12): 1869-1876.

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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 clinicopathological scores revealed that tumour MMP-9/lipocalin-2 complexes were significantly related with the classifications of Lauren 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). (C) 2007 Elsevier Ltd. All rights reserved.
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Kubben FJGM, Sier CFM, Hawinkels LJAC, et al. Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer. EUROPEAN JOURNAL OF CANCER. 2007;43(12):1869-1876.
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., et al. (2007). Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer. EUROPEAN JOURNAL OF CANCER, 43(12), 1869-1876.
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., et al. (2007). Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer. EUROPEAN JOURNAL OF CANCER 43, 1869-1876.
Kubben, F.J.G.M., et al., 2007. Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer. EUROPEAN JOURNAL OF CANCER, 43(12), p 1869-1876.
F.J.G.M. Kubben, et al., “Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer”, EUROPEAN JOURNAL OF CANCER, vol. 43, 2007, pp. 1869-1876.
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.: Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer. EUROPEAN JOURNAL OF CANCER. 43, 1869-1876 (2007).
Kubben, Frank J. G. M., Sier, Cornelis F. M., Hawinkels, Lukas J. A. C., Tschesche, Harald, van Duijn, Wim, Zuidwijk, Kim, van der Reijden, Johan J., Hanemaaijer, Roeland, Griffioen, Gerrit, Lamers, Cornelis B. H. W., and Verspaget, Hein W. “Clinical evidence for a protective role of lipocalin-2 against MDAP-9 autodegradation and the impact for gastric cancer”. EUROPEAN JOURNAL OF CANCER 43.12 (2007): 1869-1876.
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