Modulation of Tumor-host Interactions, Angiogenesis, and Tumor Growth by Tissue Inhibitor of Metalloproteinase 2 via a Novel Mechanism
| العنوان: | Modulation of Tumor-host Interactions, Angiogenesis, and Tumor Growth by Tissue Inhibitor of Metalloproteinase 2 via a Novel Mechanism |
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| المؤلفون: | Galina Baibakov, William G. Stetler-Stevenson, Sarah O'Connor, Nick G. Costouros, H. Richard Alexander, Steven K. Libutti, Dominique Lorang, Andrew L. Feldman, Vladimir Knezevic, Dong-Wan Seo, Stephen M. Hewitt, Marshall Miller |
| المصدر: | Cancer Research. 64:4481-4486 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Cancer Research, Angiogenesis, p38 mitogen-activated protein kinases, Phosphatase, Cell Cycle Proteins, Matrix metalloproteinase, Biology, p38 Mitogen-Activated Protein Kinases, Immediate-Early Proteins, Neovascularization, Mice, Transduction, Genetic, Protein Phosphatase 1, Phosphoprotein Phosphatases, medicine, Animals, Phosphorylation, Protein kinase A, Tissue Inhibitor of Metalloproteinase-2, Neovascularization, Pathologic, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Dual Specificity Phosphatase 1, Tissue inhibitor of metalloproteinase, Angiogenesis inhibitor, Mice, Inbred C57BL, Retroviridae, Oncology, Enzyme Induction, Colonic Neoplasms, Cancer research, Female, Mitogen-Activated Protein Kinases, Protein Tyrosine Phosphatases, medicine.symptom, Cell Division |
| الوصف: | Solid tumors depend on angiogenesis for sustained growth. Tissue inhibitor of metalloproteinase 2 (TIMP-2) is an angiogenesis inhibitor initially characterized for its ability to block matrix metalloproteinases; however, recent data suggest that the antiangiogenic action of TIMP-2 may rely on matrix metalloproteinase-independent mechanisms. The aim of this study was to identify molecular pathways involved in the effects of TIMP-2 on processes dependent on tumor-host interactions such as angiogenesis. Using in vitro cell culture and a syngeneic murine tumor model, we compared the effects of TIMP-2 overexpression on gene expression profiles in vitro to those observed in vivo. Validating these findings by real-time quantitative PCR and layered protein scanning, we identified up-regulation of mitogen-activated protein kinase phosphatase 1 as an effector of the antiangiogenic function of TIMP-2. Up-regulation of mitogen-activated protein kinase phosphatase 1 in tumors overexpressing TIMP-2 leads to dephosphorylation of p38 mitogen-activated protein kinase and inhibition of tumor growth and angiogenesis. Phosphatase activity appears important in regulating tumor angiogenesis, offering a promising direction for the identification of novel molecular targets and antiangiogenic compounds for the treatment of cancer. |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-03-2929 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c730dea2f3a0a1f1c7bab679707f8ed https://doi.org/10.1158/0008-5472.can-03-2929 |
| رقم الانضمام: | edsair.doi.dedup.....2c730dea2f3a0a1f1c7bab679707f8ed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/0008-5472.can-03-2929 |