title: Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas.
abstract: Fanconi anemia (FA) patients have an increased risk of head and neck squamous cell carcinoma (HNSCC) at a higher rate with no apparent risk factors. HNSCC of FA patients is an aggressive tumor characterized by multifocal origin, early metastases and frequent recurrences. Given that cancer stem cells (CSC) drive tumorigenesis, tumor recurrence and metastasis, in this study, we characterized the CSC population in FA and sporadic HNSCC. The Aldefluor assay was used to characterize and isolate CSC with high aldehyde dehydrogenase (ALDH) activity (ALDHpos) in cell lines derived from FA and sporadic HNSCC. Isolated ALDHpos and ALDHneg cells were examined for the expression of stemness genes using reverse transcription-polymerase chain reaction (RT-PCR) array. Tumor cell-derived FA and sporadic HNSCC were examined for their ability to form tumorspheres in vitro. Stem-like cell population in FA and sporadic HNSCC in human and mouse xenograft tumors were evaluated using ALDH isoform 1 (ALDH1) immunohistochemistry. FA‑HNSCC cell lines harbor a greater proportion of ALDHpos cells (15-31%) compared to sporadic HNSCC (10%). Expression of Nanog, Oct-3/4 and Stella, molecular markers of undifferentiated embryonic stem (ES) cells were detected in the ALDHpos FA‑HNSCC cells and not in the ALDHneg cells. FA‑HNSCC cell lines revealed enhanced in vitro tumorsphere formation compared to sporadic HNSCC cells. A higher percentage of ALDH1pos tumor cells are noted in the human and mouse xenograft tumors of FA‑HNSCC compared to sporadic HNSCC tumors. FA‑HNSCC are highly enriched for CSC and may serve as a model to develop CSC-targeted therapies for HNSCC.
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, TX 77054, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, TX 77054, USA.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Mu
authors.affiliation: Department of Nanomedicine and Biomedical Engineering, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Varatharasa
authors.initials: V
authors.lastname: Thiviyanathan
authors.affiliation: The Singleton Department of Pediatric Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ananth
authors.initials: A
authors.lastname: Annapragada
authors.affiliation: Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, TX 77054, USA.
authors.forename: Nadarajah
authors.initials: N
authors.lastname: Vigneswaran
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D005199:Fanconi Anemia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000150:complications / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D011506:Proteins / Q000235:genetics; D050697:Retinal Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C466105:DPPA3 protein, human; D018398:Homeodomain Proteins; D007527:Isoenzymes; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011506:Proteins; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase