Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
BMB Rep. 2018 Apr;51(4):182-187. doi: 10.5483/bmbrep.2018.51.4.185.
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling 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 responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling. Importantly, CCL2-mediated Janus kinase 1 (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 the GBM microenvironment, and reminiscent of fibroblasts in carcinoma. [BMB Reports 2018; 51(4): 182-187].
在癌中，癌症相关成纤维细胞参与力介导的细胞外基质（ECM）重塑，从而导致癌细胞的侵袭。同样，ECM 重塑在神经胶质瘤（GBM）中也积极发生，而随之而来的微环境硬度与 GBM 细胞的迁移行为密切相关。然而，在 GBM 中，负责力介导的 ECM 重塑的基质细胞仍然没有被识别。我们发现，肿瘤相关的间充质干细胞样细胞（tMSLCs）通过力介导的 ECM 重塑为 GBM 提供了一个促侵袭的基质条件。重要的是，CCL2 介导的 Janus 激酶 1（JAK1）激活增加了 tMSLCs 中肌球蛋白轻链 2 的磷酸化，导致胶原蛋白组装和肌动球蛋白收缩。总的来说，我们的研究结果表明，tMSLCs 作为基质细胞在 GBM 微环境中提供力介导的促侵袭 ECM 重塑，类似于癌中的成纤维细胞。[BMB 报告 2018;51(4):182-187]。
