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Enhanced activity of meprin-α, a pro-migratory and pro-angiogenic protease, in colorectal cancer.

التفاصيل البيبلوغرافية
العنوان: Enhanced activity of meprin-α, a pro-migratory and pro-angiogenic protease, in colorectal cancer.
المؤلفون: Daniel Lottaz, Christoph A Maurer, Agnès Noël, Silvia Blacher, Maya Huguenin, Alexandra Nievergelt, Verena Niggli, Alexander Kern, Stefan Müller, Frank Seibold, Helmut Friess, Christoph Becker-Pauly, Walter Stöcker, Erwin E Sterchi
المصدر: PLoS ONE, Vol 6, Iss 11, p e26450 (2011)
بيانات النشر: Public Library of Science (PLoS), 2011.
سنة النشر: 2011
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)-induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-α. In patients, meprin-α mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-α activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-α inhibition compared to healthy controls. In conclusion, meprin-α activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-α may promote tumor progression in colorectal cancer.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC3214016?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0026450
URL الوصول: https://doaj.org/article/0581b92e498f477c9eda68d4045d9581
رقم الأكسشن: edsdoj.0581b92e498f477c9eda68d4045d9581
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0026450