Zage Peter E, Whittle Sarah B, Shohet Jason M
Division of Hematology-Oncology, Department of Pediatrics, University of California San Diego, La Jolla, California.
Peckham Center for Cancer and Blood Disorders, Rady Children's Hospital, San Diego, California.
J Cell Biochem. 2017 Feb;118(2):221-231. doi: 10.1002/jcb.25656. Epub 2016 Aug 16.
The neural crest is a population of cells in the vertebrate embryo that gives rise to a wide range of tissues and cell types, including components of the peripheral nervous system and the craniofacial skeleton as well as melanocytes and the adrenal medulla. Aberrations in neural crest development can lead to numerous diseases, including cancers such as melanoma and neuroblastoma. Cancer stem cells (CSCs) have been identified in these neural crest-derived tumors, and these CSCs demonstrate resistance to treatment and are likely key contributors to disease relapse. Patients with neural crest-derived tumors often have poor outcomes due to frequent relapses, likely due to the continued presence of residual treatment-resistant CSCs, and therapies directed against these CSCs are likely to improve patient outcomes. CSCs share many of the same genetic and biologic features of primordial neural crest cells, and therefore a better understanding of neural crest development will likely lead to the development of effective therapies directed against these CSCs. Signaling through STAT3 has been shown to be required for neural crest development, and granulocyte colony stimulating factor (GCSF)-mediated activation of STAT3 has been shown to play a role in the pathogenesis of neural crest-derived tumors. Expression of the cell surface marker CD114 (the receptor for GCSF) has been identified as a potential marker for CSCs in neural crest-derived tumors, suggesting that CD114 expression and function may contribute to disease relapse and poor patient outcomes. Here we review the processes of neural crest development and tumorigenesis and we discuss the previously identified markers for CSC subpopulations identified in neural crest tumors and their role in neural crest tumor biology. We also discuss the potential for CD114 and downstream intracellular signaling pathways as potential targets for CSC-directed therapy. J. Cell. Biochem. 118: 221-231, 2017. © 2016 Wiley Periodicals, Inc.
神经嵴是脊椎动物胚胎中的一群细胞，可分化为多种组织和细胞类型，包括外周神经系统和颅面骨骼的组成部分，以及黑素细胞和肾上腺髓质。神经嵴发育异常可导致多种疾病，包括黑色素瘤和神经母细胞瘤等癌症。在这些源自神经嵴的肿瘤中已鉴定出癌症干细胞（CSCs），这些CSCs对治疗具有抗性，并且可能是疾病复发的关键因素。源自神经嵴的肿瘤患者由于频繁复发，预后通常较差，这可能是由于残留的抗治疗CSCs持续存在所致，针对这些CSCs的疗法可能会改善患者的预后。CSCs与原始神经嵴细胞具有许多相同的遗传和生物学特征，因此更好地了解神经嵴发育可能会导致开发针对这些CSCs的有效疗法。已证明通过STAT3信号传导是神经嵴发育所必需的，并且已证明粒细胞集落刺激因子（GCSF）介导的STAT3激活在源自神经嵴的肿瘤的发病机制中起作用。细胞表面标志物CD114（GCSF的受体）的表达已被确定为源自神经嵴的肿瘤中CSCs的潜在标志物，这表明CD114的表达和功能可能导致疾病复发和患者预后不良。在这里，我们综述了神经嵴发育和肿瘤发生的过程，并讨论了先前在神经嵴肿瘤中鉴定出的CSC亚群标志物及其在神经嵴肿瘤生物学中的作用。我们还讨论了CD114和下游细胞内信号通路作为CSC导向治疗潜在靶点的可能性。《细胞生物化学杂志》118: 221 - 231, 2017。© 2016威利期刊公司。
