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Force-mediated proinvasive matrix remodeling driven by tumor-associated mesenchymal stem-like cells in glioblastoma
Eun-Jung Lim1,#, Yongjoon Suh1,#, Seungmo Kim1, Seok-Gu Kang2, Su-Jae Lee1,*
1Life Science, Hanyang University,
2Neurosurgery, Yonsei University College of Medicine
Abstract
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling is actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells being responsible for force-mediated ECM remodeling remain unidentified. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide proinvasive matrix condition in GBM by force-mediated ECM remodeling. Importantly, CCL2-mediated JAK1 activation increased phosphorylation of myosin light chain 2 in tMSLCs and led to collagen assembly and actomyosin contractility. Collectively, our findings implicate tMSLCs as stromal cells providing force-mediated proinvasive ECM remodeling in GBM microenvironment, being reminiscent of fibroblasts in carcinoma.
Abstract, Accepted Manuscript(in press) [Submitted on September 15, 2017, Accepted on December 4, 2017]
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