دورية أكاديمية
G-CSF receptor positive neuroblastoma subpopulations are enriched in chemotherapy-resistant or relapsed tumors and are highly tumorigenic.
| العنوان: | G-CSF receptor positive neuroblastoma subpopulations are enriched in chemotherapy-resistant or relapsed tumors and are highly tumorigenic. |
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| المؤلفون: | Hsu DM; Division of Pediatric Surgery, Michael E DeBakey Department of Surgery, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA., Agarwal S, Benham A, Coarfa C, Trahan DN, Chen Z, Stowers PN, Courtney AN, Lakoma A, Barbieri E, Metelitsa LS, Gunaratne P, Kim ES, Shohet JM |
| المصدر: | Cancer research [Cancer Res] 2013 Jul 01; Vol. 73 (13), pp. 4134-46. Date of Electronic Publication: 2013 May 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Drug Resistance, Neoplasm*, Cell Transformation, Neoplastic/*metabolism , Neoplasm Recurrence, Local/*metabolism , Neuroblastoma/*metabolism , Receptors, Granulocyte Colony-Stimulating Factor/*metabolism, Animals ; Cell Differentiation ; Cell Line, Tumor ; Female ; Granulocyte Colony-Stimulating Factor/physiology ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; MicroRNAs/genetics ; MicroRNAs/metabolism ; N-Myc Proto-Oncogene Protein ; Neoplasm Transplantation ; Neoplastic Stem Cells/metabolism ; Neuroblastoma/drug therapy ; Neuroblastoma/pathology ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Proto-Oncogene Proteins/genetics ; STAT3 Transcription Factor/metabolism ; Side-Population Cells/metabolism ; Transcriptome ; Tumor Suppressor Protein p53/metabolism |
| مستخلص: | Neuroblastoma is a neural crest-derived embryonal malignancy, which accounts for 13% of all pediatric cancer mortality, primarily due to tumor recurrence. Therapy-resistant cancer stem cells are implicated in tumor relapse, but definitive phenotypic evidence of the existence of these cells has been lacking. In this study, we define a highly tumorigenic subpopulation in neuroblastoma with stem cell characteristics, based on the expression of CSF3R, which encodes the receptor for granulocyte colony-stimulating factor (G-CSF). G-CSF receptor positive (aka G-CSFr(+) or CD114(+)) cells isolated from a primary tumor and the NGP cell line by flow cytometry were highly tumorigenic and capable of both self-renewal and differentiation to progeny cells. CD114(+) cells closely resembled embryonic and induced pluripotent stem cells with respect to their profiles of cell cycle, miRNA, and gene expression. In addition, they reflect a primitive undifferentiated neuroectodermal/neural crest phenotype revealing a developmental hierarchy within neuroblastoma tumors. We detected this dedifferentiated neural crest subpopulation in all established neuroblastoma cell lines, xenograft tumors, and primary tumor specimens analyzed. Ligand activation of CD114 by the addition of exogenous G-CSF to CD114(+) cells confirmed intact STAT3 upregulation, characteristic of G-CSF receptor signaling. Together, our data describe a novel distinct subpopulation within neuroblastoma with enhanced tumorigenicity and a stem cell-like phenotype, further elucidating the complex heterogeneity of solid tumors such as neuroblastoma. We propose that this subpopulation may represent an additional target for novel therapeutic approaches to this aggressive pediatric malignancy. (©2013 AACR.) |
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| معلومات مُعتمدة: | K08 CA090517 United States CA NCI NIH HHS; L40 CA142347 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (MYCN protein, mouse) 0 (MicroRNAs) 0 (N-Myc Proto-Oncogene Protein) 0 (Proto-Oncogene Proteins) 0 (Receptors, Granulocyte Colony-Stimulating Factor) 0 (STAT3 Transcription Factor) 0 (STAT3 protein, human) 0 (TP53 protein, human) 0 (Tumor Suppressor Protein p53) 143011-72-7 (Granulocyte Colony-Stimulating Factor) |
| تواريخ الأحداث: | Date Created: 20130521 Date Completed: 20130904 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4298227 |
| DOI: | 10.1158/0008-5472.CAN-12-4056 |
| PMID: | 23687340 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-12-4056 |