title: CD98 marks a subpopulation of head and neck squamous cell carcinoma cells with stem cell properties.
abstract: Patients with advanced head and neck squamous cell carcinomas (HNSCCs) are often treated with concomitant chemotherapy and radiotherapy, but only 50% is cured. A possible explanation for treatment failure is therapy resistance of the cancer stem cells (CSCs). The application of compounds specifically targeting these CSCs, in addition to routinely used therapeutics, would likely improve clinical outcome. We demonstrate that the previously described monoclonal antibody K984 recognizes the CD98 cell surface protein, which is specifically expressed by cells forming the squamous basal cell layer, the region where the squamous stem cells reside. Moreover, CD98 is highly resistant to the proteolytic enzymes required for CSC enrichment procedures. We show that CD98(high) cells, in contrast to CD98(low) cells, are able to generate tumors in immunodeficient mice, indicating that CD98(high) cells have stem cell characteristics. Furthermore, the CD98(high) subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98(low) fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor. CD98 is a promising CSC enrichment marker in HNSCC. Our data support the CSC concept in head and neck cancer and the potential relevance of these cells for treatment outcome.
authors.affiliation: Department of Otolaryngology/Head-Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sanne R
authors.initials: SR
authors.lastname: Martens-de Kemp
authors.forename: Arjen
authors.initials: A
authors.lastname: Brink
authors.forename: Marijke
authors.initials: M
authors.lastname: Stigter-van Walsum
authors.forename: J Mirjam A
authors.initials: JM
authors.lastname: Damen
authors.forename: François
authors.initials: F
authors.lastname: Rustenburg
authors.forename: Thijs
authors.initials: T
authors.lastname: Wu
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Schuurhuis
authors.forename: Boudewijn J M
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: Monique
authors.initials: M
authors.lastname: Slijper
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D027261:Fusion Regulatory Protein-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome; D014183:Transplantation, Heterologous
chemical_list: D027261:Fusion Regulatory Protein-1; D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering