Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP-3
| العنوان: | Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP-3 |
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| المؤلفون: | J. Dinesh Kumar, Christopher Holmberg, Péter Hegyi, Timothy C. Wang, Andrea Varro, Kris Gevaert, Graham J. Dockray, Nicole Cash, Francis Impens, Bart Ghesquière, Sandhir Kandola |
| المصدر: | JOURNAL OF PROTEOME RESEARCH Journal of Proteome Research |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | PROTEOMICS DATA, MATRIX METALLOPROTEINASE-7, PROGRESSION, Matrix metalloproteinase, Biochemistry, Mice, 0302 clinical medicine, Stable isotope labeling by amino acids in cell culture, Tumor Microenvironment, Myofibroblasts, 0303 health sciences, medicine.diagnostic_test, N-TERMINAL PEPTIDES, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Matrix Metalloproteinase 2, GROWTH, Matrix Metalloproteinase 3, Matrix Metalloproteinase 1, Myofibroblast, Proteases, FIBROBLASTS, Stromal cell, Proteolysis, Biology, Article, 03 medical and health sciences, neo-N-termini, Stomach Neoplasms, HELICOBACTER-PYLORI, medicine, Animals, Humans, degradome, 030304 developmental biology, Cell Proliferation, IDENTIFICATION, Cancer, Biology and Life Sciences, General Chemistry, medicine.disease, Molecular biology, Xenograft Model Antitumor Assays, myofibroblast, secretome, Cancer cell, CELLS, Cancer research, TUMOR STROMA, COFRADIC |
| الوصف: | Cancer progression involves changes in extracellular proteolysis, but the contribution of stromal cell secretomes to the cancer degradome remains uncertain. We have now defined the secretome of a. specific stromal cell type, the rnyofibroblast, in gastric cancer and its modification by proteolysis. SILAC labeling and COFRADIC isolation of methionine containing peptides allowed us to quantify differences in gastric cancer-derived myofibroblasts compared with myofibroblasts from adjacent tissue, revealing increased abundance of several proteases in cancer myofibroblasts including matrix metalloproteinases (MMP)-1 and -3. Moreover, N-terminal COFRADIC analysis identified cancer-restricted proteolytic cleavages, including liberation of the active forms of MMP-1, -2, and -3 from their inactive precursors. In vivo imaging confirmed increased MMP activity when gastric cancer cells were xenografted in mice together with gastric cancer myofibroblasts. Western blot and enzyme activity assays confirmed increased MMP-1, -2, and -3 activity in cancer myofibroblasts, and cancer cell migration assays indicated stimulation by MMP-1, -2, and -3 in cancer-associated rnyofibroblast media. Thus, cancer-derived myofibroblasts differ from their normal counterparts by increased production and activation of MMP-1, -2, and -3, and this may contribute to the remodelling of the cancer cell microenvironment. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1535-3893 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e94abbf38bdbda54ba15747ac00dd969Test https://hdl.handle.net/1854/LU-4223831Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e94abbf38bdbda54ba15747ac00dd969 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15353893 |
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