Chemically-induced Neurite-like Outgrowth Reveals Multicellular Network Function in Patient-derived Glioblastoma Cells
Citations Over Time
Abstract
Summary 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. We show that small molecule inhibition of RHO-associated serine/threonine kinase (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 calcium 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.
Related Papers
- → Bacterial solutions to multicellularity: a tale of biofilms, filaments and fruiting bodies(2014)511 cited
- → Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth(2011)78 cited
- → The influence of surface protease activity on neuritogenesis and neurite retraction is dependent upon mode of neurite induction: Inhibition of thrombin-mediated surface protease activity is cruicial for neurite outgrowth but not for maintenance of existin(1996)1 cited
- → Long Term Neurite Outgrowth Enhancing Effect and Neurite Regeneration Effect of an Active Substance from a Brown Alga Sargassum Macrocarpum on Rat Pheochromocytoma PC12D Cells(2002)
- α-Synuclein Promotes Neurite Outgrowth of Primarily Cultured Rat Brain Neurons(2009)