ADAM8 affects glioblastoma progression by regulating osteopontin-mediated angiogenesis
| Autor: | Vanessa Rothbart, Jörg W. Bartsch, Songbo Guo, Christopher Nimsky, Helena Guerreiro, Caroline Driescher, Uwe Schlomann, Catharina Conrad, Barbara Carl, Yu Li, Kai Zhao, Axel Pagenstecher, Miriam Bopp, Alexander König |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Angiogenesis Clinical Biochemistry medicine.disease_cause Biochemistry 03 medical and health sciences 0302 clinical medicine Immune system Glioma medicine Osteopontin U87 Molecular Biology Tumor microenvironment Microglia biology business.industry medicine.disease nervous system diseases 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biology.protein Carcinogenesis business |
| Zdroj: | Biological Chemistry. 402:195-206 |
| ISSN: | 1437-4315 1431-6730 |
| DOI: | 10.1515/hsz-2020-0184 |
| Popis: | Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|