Crosstalk between GBM cells and mesenchymal stemlike cells promotes the invasiveness of GBM through the C5a/p38/ZEB1 axis
| العنوان: | Crosstalk between GBM cells and mesenchymal stemlike cells promotes the invasiveness of GBM through the C5a/p38/ZEB1 axis |
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| المؤلفون: | Yong Min Huh, Jin Kyoung Shim, Jun Jeong Choi, Jong Hee Chang, Myung Jin Park, Junghwa Cha, Eun Jung Lim, Yongjoon Suh, Pilnam Kim, Rae Kwon Kim, Seok Gu Kang, Neha Kaushik, Se Hoon Kim, Hae June Lee, Yoonjee Oh, Min Jung Kim, Su Jae Lee, Ji Hyun Lee, Yong Kil Hong, Seungmo Kim |
| المصدر: | Neuro-Oncology. 22:1452-1462 |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Cancer Research, Tumor microenvironment, Stromal cell, Mesenchymal stem cell, Complement factor I, Biology, medicine.disease, Paracrine signalling, Oncology, Glioma, Cancer research, medicine, Neurology (clinical), Signal transduction |
| الوصف: | Background Mesenchymal stemlike cells (MSLCs) have been detected in many types of cancer including brain tumors and have received attention as stromal cells in the tumor microenvironment. However, the cellular mechanisms underlying their participation in cancer progression remain largely unexplored. The aim of this study was to determine whether MSLCs have a tumorigenic role in brain tumors. Methods To figure out molecular and cellular mechanisms in glioma invasion, we have cultured glioma with MSLCs in a co-culture system. Results Here, we show that MSLCs in human glioblastoma (GBM) secrete complement component C5a, which is known for its role as a complement factor. MSLC-secreted C5a increases expression of zinc finger E-box-binding homeobox 1 (ZEB1) via activation of p38 mitogen-activated protein kinase (MAPK) in GBM cells, thereby enhancing the invasion of GBM cells into parenchymal brain tissue. Conclusion Our results reveal a mechanism by which MSLCs undergo crosstalk with GBM cells through the C5a/p38 MAPK/ZEB1 signaling loop and act as a booster in GBM progression. Key Points 1. MSLCs activate p38 MAPK-ZEB1 signaling in GBM cells through C5a in a paracrine manner, thereby boosting the invasiveness of GBM cells in the tumor microenvironment. 2. Neutralizing of C5a could be a potential therapeutic target for GBM by inhibition of mesenchymal phenotype. |
| تدمد: | 1523-5866 1522-8517 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::ef86fdc33c9e3438ea8344725671d3cb https://doi.org/10.1093/neuonc/noaa064 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........ef86fdc33c9e3438ea8344725671d3cb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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