title: In vitro evaluation of sialyl Lewis X relationship with head and neck cancer stem cells.
abstract: OBJECTIVE
  To evaluate in vitro the potential links between sialyl Lewis X (sLeX) and cancer stem cells (CSC) in head and neck squamous cell carcinoma (HNSCC). HNSCC is an aggressive malignancy with high mortality mainly due to metastasis. CSC have emerged as important players in HNSCC metastasis. sLeX is a tetrasaccharide carbohydrate known to play a key role in metastatic dissemination by promoting binding of the tumor cells to the endothelium.
  
  
  METHODS
  Experimental, in vitro.
  
  
  METHODS
  Laboratory of Head and Neck Cancer Metastasis, University of Michigan.
  
  
  METHODS
  A panel of stage- and anatomic-site specific primary and metastatic HNSCC cell lines was assessed by flow cytometry to quantify sLeX relative expression levels. Serum-free conditioned media from the same HNSCC lines was collected over a time course of 72 hours and assessed by Western blot for secreted sLeX expression. Representative HNSCC cell lines were cultured as floating orospheres (condition that enhance CSC growth) or under normal adherent conditions and characterized by flow cytometry for CSC markers (CD44, aldehyde dehydrogenase [ALDH]) comparatively with sLeX expression.
  
  
  RESULTS
  sLeX is predominantly expressed in carcinomas originating from the oral cavity. Secreted sLeX is also found to be high in oral carcinomas and increased over the analyzed time course. Floating orospheres were strongly positive for CD44 and ALDH, confirming CSC enrichment of the orospheres. Tumor cells grown as orospheres are 95% to 100% positive for sLeX compared to 10% to 40% of adherent counterpart.
  
  
  CONCLUSIONS
  These studies provide the first evidence of sLeX relationship with CSC in HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Ann Arbor, Michigan 48109-5616, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Czerwinski
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Desiderio
authors.forename: Omar
authors.initials: O
authors.lastname: Shkeir
authors.forename: Petros
authors.initials: P
authors.lastname: Papagerakis
authors.forename: Martian C
authors.initials: MC
authors.lastname: Lapadatescu
authors.forename: John H
authors.initials: JH
authors.lastname: Owen
authors.forename: Maria
authors.initials: M
authors.lastname: Athanassiou-Papaefthymiou
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Papaccio
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.forename: Silvana
authors.initials: S
authors.lastname: Papagerakis
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009844:Oligosaccharides / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
chemical_list: D018960:Hyaluronan Receptors; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D000444:Aldehyde Dehydrogenase
keywords: CD44; head and neck squamous cell carcinomas; in vitro analysis; sLeX (sialyl Lewis X); stem cells
references.citation: FASEB J. 2013 Jan;27(1):13-24
references.pmid: 23024375
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63
references.pmid: 17548814
references.citation: Cancer Res. 1993 Aug 1;53(15):3632-7
references.pmid: 8101764
references.citation: Head Neck. 2013 Nov;35(11):1542-50
references.pmid: 23322448
references.citation: Oncogene. 2004 Sep 20;23(43):7274-82
references.pmid: 15378087
references.citation: Cancer Res. 2003 Sep 15;63(18):5821-8
references.pmid: 14522905
references.citation: Semin Cancer Biol. 1993 Oct;4(5):319-24
references.pmid: 7903054
references.citation: Neoplasma. 2009;56(1):40-7
references.pmid: 19152244
references.citation: Cancer Res. 2006 Feb 15;66(4):1883-90; discussion 1895-6
references.pmid: 16488983
references.citation: Nature. 2001 Nov 1;414(6859):105-11
references.pmid: 11689955
references.citation: Head Neck. 2010 Sep;32(9):1195-201
references.pmid: 20073073
references.citation: Nature. 2007 Jan 4;445(7123):106-10
references.pmid: 17122772
references.citation: Cancer. 1994 Mar 15;73(6):1552-61
references.pmid: 7908856
references.citation: Oral Oncol. 2012 Jan;48(1):26-32
references.pmid: 22014666
references.citation: Nat Rev Cancer. 2004 Jun;4(6):448-56
references.pmid: 15170447
references.citation: Cancer Res. 2010 Dec 1;70(23):9969-78
references.pmid: 21098716
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Curr Opin Genet Dev. 2008 Feb;18(1):48-53
references.pmid: 18356041
references.citation: Hum Pathol. 2009 Sep;40(9):1320-9
references.pmid: 19386346
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Arch Otolaryngol Head Neck Surg. 2010 Dec;136(12):1260-6
references.pmid: 21173377
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: Dis Colon Rectum. 2001 Jun;44(6):876-84
references.pmid: 11391152
references.citation: Methods Mol Biol. 2012;879:513-29
references.pmid: 22610581
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
references.pmid: 17210912
references.citation: Front Endocrinol (Lausanne). 2012 Aug 03;3:90
references.pmid: 22876238
references.citation: Surg Oncol Clin N Am. 2001 Apr;10(2):243-55, vii
references.pmid: 11382585
references.citation: Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):135-46
references.pmid: 22507326
references.citation: Urol Int. 2000;64(3):129-33
references.pmid: 10859542
references.citation: Cancer Res. 2005 Dec 1;65(23):10946-51
references.pmid: 16322242
references.citation: Hum Pathol. 2004 Jan;35(1):75-85
references.pmid: 14745728
references.citation: Hepatology. 2006 Jul;44(1):240-51
references.pmid: 16799977
references.citation: J Leukoc Biol. 1985 Apr;37(4):407-22
references.pmid: 3855947
references.citation: Cancer Res. 2007 Feb 1;67(3):1030-7
references.pmid: 17283135
references.citation: Annu Rev Cell Dev Biol. 2007;23:675-99
references.pmid: 17645413
references.citation: Head Neck. 2013 Jul;35(7):1015-21
references.pmid: 22791367
references.citation: J Clin Gastroenterol. 2002 Apr;34(4):408-15
references.pmid: 11907351