Ayuso-Sacido Angel, Graham Christopher, Greenfield Jeff P, Boockvar John A
Neurosurgical Laboratory for Translational Stem Cell Research, Department of Neurosurgery, Weill Cornell Medical College of Cornell University, New York, NY, USA.
Curr Stem Cell Res Ther. 2006 Sep;1(3):387-94. doi: 10.2174/157488806778226849.
Recruitment of neural stem cells (NSCs) represents an elegant strategy for replacing adult central nervous system (CNS) cells lost to injury or disease. However, except in the rostral migratory stream to the olfactory bulb, the adult CNS harbors a relatively non permissive environment for motility of neural stem cells. This opens the possibility of therapeutic enhancement of NSC motility towards sites of CNS injury or disease. The Epidermal Growth Factor Receptor (EGFR) is involved in the activation of a number of downstream pathways that regulate the phenotype of progenitor cells. Activated EGFR tyrosine kinase activity enhances NSC migration, proliferation, and survival. However, EGFR signaling is also known to play a role in the most malignant and highly invasive of human tumors, glioblastoma multiforme (GBM). Recent evidence supports the theory that GBM derives from a 'cancer stem cell' and that EGFR signals are commonly altered in these precursor cells. This article will review the role of EGFR signaling as it relates to neural stem cell motility and invasion. The duality of altered EGFR signaling in neural progenitor cells is discussed and opportunities for enhancing the recruitment of adult progenitors, and consequences of altering EGFR signaling in progenitor cells will be highlighted.
招募神经干细胞（NSCs）是一种巧妙的策略，可用于替代因损伤或疾病而损失的成体中枢神经系统（CNS）细胞。然而，除了向嗅球的吻侧迁移流外，成体CNS对神经干细胞的运动性而言是一个相对不利的环境。这为通过治疗手段增强神经干细胞向CNS损伤或疾病部位的运动性提供了可能性。表皮生长因子受体（EGFR）参与了许多调节祖细胞表型的下游信号通路的激活。激活的EGFR酪氨酸激酶活性可增强神经干细胞的迁移、增殖和存活。然而，EGFR信号传导在人类最恶性、侵袭性最强的肿瘤——多形性胶质母细胞瘤（GBM）中也发挥作用。最近的证据支持这样一种理论，即GBM源自“癌症干细胞”，并且EGFR信号在这些前体细胞中通常会发生改变。本文将综述EGFR信号传导与神经干细胞运动性和侵袭性相关的作用。文中将讨论神经祖细胞中EGFR信号改变的双重性，并着重介绍增强成体祖细胞招募的机会以及改变祖细胞中EGFR信号传导的后果。
