{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T19:33:55Z","timestamp":1771011235138,"version":"3.50.1"},"reference-count":46,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2012,12]]},"abstract":"\nObject<\/jats:title>\nTumor-initiating cells are uniquely resilient to current treatment modalities and play an important role in tumor resistance and recurrence. The lack of specific tumor-initiating cell markers to identify and target these cells presents a major obstacle to effective directed therapy.<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nTo identify tumor-initiating cell markers in primary brain tumors, the authors compared the proteomes of glioma tumor-initiating cells to their differentiated progeny using a novel, nongel\/shotgun-based, multidimensional liquid-chromatography protein separation technique. An in vivo xenograft model was used to demonstrate the tumorigenic and stem cell properties of these cells. Western blot and immunofluorescence analyses were used to confirm findings of upregulated ciliary neurotrophic factor receptor subunit\u2013\u03b1 (CNTFR\u03b1) in undifferentiated tumor-initiating cells and gliomas of increasing tumor grade. Sequencing of the CNTFR\u03b1<\/jats:italic> coding regions was performed for mutation analysis. Finally, antibody-dependent cell-mediated cytotoxicity was used to establish the role of CNTFR\u03b1 as a potential immunotherapeutic target.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nCiliary neurotrophic factor receptor subunit\u2013\u03b1 expression was increased in tumor-initiating cells and was decreased in the cells' differentiated progeny, and expression levels increased with glioma grade. Mutations of CNTFR\u03b1<\/jats:italic> are not common in gliomas. Functional studies using CNTF treatment in glioma tumor-initiating cells showed induction of differentiation through the CNTFR\u03b1 pathway. Treatment with anti-CNTFR\u03b1 antibody resulted in increased antibody-dependent cell-mediated cytotoxicity in CNTFR\u03b1 expressing DAOY cells but not in cell lines that lack CNTFR\u03b1.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nThese data indicate that CNTFR\u03b1 plays a role in the formation or maintenance of tumor-initiating cells in gliomas, is a marker that correlates with histological grade, may underlie treatment resistance in some cases, and is a potential therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2012.9.jns1212","type":"journal-article","created":{"date-parts":[[2012,10,12]],"date-time":"2012-10-12T14:06:18Z","timestamp":1350050778000},"page":"1022-1031","source":"Crossref","is-referenced-by-count":18,"title":["CNTF receptor subunit \u03b1 as a marker for glioma tumor-initiating cells and tumor grade"],"prefix":"10.3171","volume":"117","author":[{"given":"Jie","family":"Lu","sequence":"first","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Ksendzovsky","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunzhang","family":"Yang","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautam U.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymund L.","family":"Yong","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Weil","sequence":"additional","affiliation":[{"name":"Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Neurosurgery, The Neurological Institute, Cleveland Clinic, Cleveland, Ohio; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deric M.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry M.","family":"Mushlin","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueping","family":"Fang","sequence":"additional","affiliation":[{"name":"Calibrant Biosystems, Gaithersburg, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M.","family":"Balgley","sequence":"additional","affiliation":[{"name":"Calibrant Biosystems, Gaithersburg, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Calibrant Biosystems, Gaithersburg, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell R.","family":"Lonser","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengping","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-jns1212","series-title":"Curr Opin Genet Dev","first-page":"43","article-title":"Therapeutic implications of cancer stem cells","volume":"14","author":"Al-Hajj","year":"2004"},{"key":"b2-jns1212","series-title":"Oncogene","first-page":"7274","article-title":"Self-renewal and solid tumor stem cells","volume":"23","author":"Al-Hajj","year":"2004"},{"key":"b3-jns1212","series-title":"Proc Natl Acad Sci U S A","first-page":"3983","article-title":"Prospective identification of tumorigenic breast cancer 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multiple endocrine neoplasia type 2-associated pheochromocytomas","volume":"90","author":"Vogel","year":"2005"},{"key":"b42-jns1212","series-title":"World J Gastroenterol","first-page":"3933","article-title":"Prognostic significance of erythropoietin and erythropoietin receptor in gastric adenocarcinoma","volume":"17","author":"Wang","year":"2011"},{"key":"b43-jns1212","series-title":"Anal Chem","first-page":"6549","article-title":"Proteome analysis of microdissected tumor tissue using a capillary isoelectric focusing-based multidimensional separation platform coupled with ESI-tandem MS","volume":"77","author":"Wang","year":"2005"},{"key":"b44-jns1212","series-title":"J Neurooncol","first-page":"243","article-title":"CNTF and its receptor subunits in human gliomas","volume":"44","author":"Weis","year":"1999"},{"key":"b45-jns1212","series-title":"Oncogene","first-page":"3454","article-title":"Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway 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investigation"],"short-title":[],"issued":{"date-parts":[[2012,12]]},"references-count":46,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2012.9.jns1212","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12]]}}}