Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA; Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA; Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China.
Cell Rep. 2014 Jan 16;6(1):117-29. doi: 10.1016/j.celrep.2013.11.043. Epub 2013 Dec 27.
Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal brain versus GBM. Targeting JAM-A compromised the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that GBM-targeting strategies can be identified through screening adhesion receptors and JAM-A represents a mechanism for niche-driven CSC maintenance.
干细胞存在于调节自我更新和分化平衡的龛位中。干细胞的特性与其通过黏附机制与龛位相互作用的能力有关。为了鉴定破坏癌症干细胞（CSC）黏附的靶点，我们对源自胶质母细胞瘤（GBM）患者的细胞进行了流式细胞术筛选，并鉴定出连接黏附分子 A（JAM-A）是CSC 自我更新和肿瘤生长所必需的黏附机制。JAM-A 对于正常神经干细胞/祖细胞（NPC）功能是可有可无的，且 JAM-A 在正常大脑与 GBM 中的表达减少。靶向 JAM-A 会损害 CSCs 的自我更新能力。JAM-A 的表达与 GBM 患者的预后呈负相关。我们的研究结果表明，可以通过筛选黏附受体来鉴定针对 GBM 的靶向策略，而 JAM-A 则代表了龛位驱动 CSC 维持的机制。
