ADAM12 is expressed in the tumour vasculature and mediates ectodomain shedding of several membrane-anchored endothelial proteins
| العنوان: | ADAM12 is expressed in the tumour vasculature and mediates ectodomain shedding of several membrane-anchored endothelial proteins |
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| المؤلفون: | Marie Kveiborg, Julie B. Noer, Jens Berthelsen, Pauliina Kronqvist, Marie Christine Klitgaard, Reidar Albrechtsen, Alexander Kotzsch, Carl P. Blobel, Ulla M. Wewer, Camilla Fröhlich, Camilla Nehammer |
| المصدر: | Biochemical Journal. 452:97-109 |
| بيانات النشر: | Portland Press Ltd., 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | ADAM12 Protein, Breast Neoplasms, Biology, ta3111, Biochemistry, Mice, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, Disintegrin, Animals, Humans, Molecular Biology, Cell Line, Transformed, Mice, Knockout, Neovascularization, Pathologic, Cell adhesion molecule, HEK 293 cells, Membrane Proteins, Cell Biology, ADAM Proteins, Gene Expression Regulation, Neoplastic, Endothelial stem cell, Vascular endothelial growth factor B, HEK293 Cells, Ectodomain, Membrane protein, Cancer research, biology.protein, Female |
| الوصف: | ADAM (a disintegrin and metalloproteinase) 12 is a metalloprotease implicated in cancer progression. ADAM12 can activate membrane-anchored proteins, such as sonic hedgehog, Delta-like 1 and certain epidermal growth factor receptor ligands, through a process called ectodomain shedding. We screened several membrane-anchored proteins to further dissect the substrate profile of ADAM12-mediated ectodomain shedding, and found shedding of five previously unreported substrates [Kitl1, VE-cadherin (vascular endothelial cadherin), Flk-1 (fetal liver kinase 1), Tie-2, and VCAM-1 (vascular cell adhesion molecule 1)], of which the latter four are specifically expressed by endothelial cells. We also observed that ADAM12 expression was increased in the tumour vasculature of infiltrating ductal carcinoma of the human breast as compared with little to no expression in normal breast tissue vasculature, suggesting a role for ADAM12 in tumour vessels. These results prompted us to further evaluate ADAM12-mediated shedding of two endothelial cell proteins, VE-cadherin and Tie-2. Endogenous ADAM12 expression was very low in cultured endothelial cells, but was significantly increased by cytokine stimulation. In parallel, the shed form of VE-cadherin was elevated in such cytokine-stimulated endothelial cells, and ADAM12 siRNA (small interfering RNA) knockdown reduced cytokine-induced shedding of VE-cadherin. In conclusion, the results of the present study demonstrate a role for ADAM12 in ectodomain shedding of several membrane-anchored endothelial proteins. We speculate that this process may have importance in tumour neovascularization or/and tumour cell extravasation. |
| تدمد: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20121558 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd6cad5552e52730cc4bbc05af58c4c2 https://doi.org/10.1042/bj20121558 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....cd6cad5552e52730cc4bbc05af58c4c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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| DOI: | 10.1042/bj20121558 |