title: CD114: A New Member of the Neural Crest-Derived Cancer Stem Cell Marker Family.
abstract: 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.
authors.affiliation: 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.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Zage
authors.affiliation: Department of Pediatrics, Section of Hematology-Oncology, Children's Cancer Center, Houston, Texas.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Whittle
authors.affiliation: Department of Pediatrics, Section of Hematology-Oncology, Children's Cancer Center, Houston, Texas.|Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Shohet
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009432:Neural Crest / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: CD114; GCSF; MELANOMA; NEUROBLASTOMA; STAT3