دورية أكاديمية
Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells
| العنوان: | Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells |
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| المؤلفون: | da Silva, Barbara, Irving, Bronwyn K., Polson, Euan S., Droop, Alastair, Griffiths, Hollie B. S., Mathew, Ryan K., Stead, Lucy F., Marrison, Joanne, Williams, Courtney, Williams, Jennifer, Short, Susan C., Scarcia, Margherita, O'Toole, Peter J., Allison, Simon J., Mavria, Georgia, Wurdak, Heiko |
| بيانات النشر: | The Company of Biologists Ltd |
| سنة النشر: | 2019 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | SHORT REPORT |
| الوصف: | Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo -induced cellular network (iNet) ‘webs’, which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo , and may thereby accelerate future studies into the biology of GBM cellular networks. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://jcs.biologists.org/cgi/content/short/132/19/jcs228452Test; http://dx.doi.org/10.1242/jcs.228452Test |
| DOI: | 10.1242/jcs.228452 |
| الإتاحة: | https://doi.org/10.1242/jcs.228452Test http://jcs.biologists.org/cgi/content/short/132/19/jcs228452Test |
| حقوق: | Copyright (C) 2019, Company of Biologists |
| رقم الانضمام: | edsbas.FCC48F2D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1242/jcs.228452 |
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