کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8304449 | 1538409 | 2016 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Impact of cathepsin B on the interstitial fluid proteome of murine breast cancers
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کلمات کلیدی
CtsBPyMTLC-MS/MS - LC-MS / MSscx - اسکاstrong cation exchange - تبادل کاتیون قویEctodomain shedding - ریزش اکتودومینliquid chromatography tandem-mass spectrometry - طیف سنجی جرمی کروماتوگرافی مایعinterstitial fluid - مایع بینابینیTumor microenvironment - میکرو محیط زیست تومورProteases - پروتئازProteomics - پروتئومیکسCathepsins - کاتهپسین ها
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Carcinomas establish a molecular cross talk between malignant tumor cells and the activated non-malignant cells of the tumor stroma. This cell-cell communication in tumor-stroma interaction includes soluble, secreted proteins that act in a paracrine or autocrine manner. Proteases are crucial factors in tumor-stroma interaction by degrading or truncating secreted bioactive proteins. The cysteine protease cathepsin B is frequently overexpressed in several cancer types, including breast cancer. Its abundance often correlates with poor prognosis. In the murine polyoma virus middle T oncogene (PyMT) breast cancer model, cathepsin B is equally pro-tumorigenic. In this study, we investigate how cathepsin B shapes the secreted proteome of PyMT breast cancers. We employed a novel strategy to harvest tumor interstitial fluid (IF) in combination with chemical stable isotope tagging for quantitative proteomic comparison of IF stemming from PyMT tumors from wild-type mice, mice lacking cathepsin B, and mice over-expressing human cathepsin B. In three biological replicates, we achieve good proteome coverage (â¼1700 proteins), with a large content (>70%) of secreted proteins. This characterizes IF as a robust source for the investigation of cancer secretomes. We also identified a large number of shed ectodomains, thus highlighting the importance of tumor-contextual cell surface proteolysis. Furthermore, IF contained >190 proteases and protease inhibitors, which span the entire range of absolute protein abundances; an observation testifying for an important role of proteolysis in tumor-stroma interaction. The cathepsin B genotype consistently affected proteins including alpha-1B-glycoprotein and major urinary proteins 11 and 8 (MUP8). Our study establishes tumor IF as a rich source for the investigation of secreted proteins in tumor biology and sheds light on complex proteolytic networks in the breast cancer secretome.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 122, March 2016, Pages 88-98
Journal: Biochimie - Volume 122, March 2016, Pages 88-98
نویسندگان
Alejandro Gomez-Auli, Larissa Elisabeth Hillebrand, Martin Lothar Biniossek, Christoph Peters, Thomas Reinheckel, Oliver Schilling,