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. 2015 Oct;10(4):2289-2294.
doi: 10.3892/ol.2015.3542. Epub 2015 Jul 29.

Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification

Martin Leinung  1 , Benjamin Ernst  1 , Constanze Döring  2 , Jens Wagenblast  1 , Aykut Tahtali  1 , Marc Diensthuber  1 , Timo Stöver  1 , Christin Geissler  1
Affiliations

Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification

Martin Leinung et al. Oncol Lett. 2015 Oct.

Abstract

In head and neck squamous cell carcinoma (HNSCC), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and hyaluronan receptor cluster of differentiation 44 (CD44) are often used as cancer stem cell (CSC) markers. The aim of the present study was to examine the relevance of these proteins for HNSCC in general and for the identification of CSCs. Tumors from 48 patients with primary HNSCC were analyzed for the expression of ALDH1A1 and CD44. Additionally, the association of the proteins with the proliferation rate and epidermal growth factor receptor (EGFR) expression was analyzed. ALDH1A1 was expressed in 54.2% of the carcinoma samples while CD44 was expressed in 89.6% of the carcinoma samples. Most notably, these proteins were often not expressed exclusively in a subpopulation, but also in the majority of tumor cells (ALDH1A1: 30.8% of ALDH1A1+ tumors; CD44: 65.1% of CD44+ tumors). Furthermore, patients with ALDH1A1+ tumors exhibited worse survival rates. CD44 and EGFR expression patterns were overlapping within the tumors and the expression rates were significantly connected. Ki-67+ tumor cells often expressed CD44. ALDH1A1 and CD44 expression patterns only partly overlapped. Consequently, ALDH1A1 and CD44 play significant roles in carcinogenesis and tumor progression. Within the present study, CD44 appeared to interact with EGFR and was more often expressed in primary HNSCC than the marker ALDH1A1. However, ALDH1A1 was a better marker to define a subpopulation of tumor cells. Finally, neither ALDH1A1 nor CD44, alone or combined, were sufficient to determine the CSC population in HNSCC.

Keywords: ALDH1A1; CD44; cancer stem cells; head and neck squamous cell carcinoma.

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Figures

Figure 1.
Figure 1.
Immunohistochemistry of human primary tumors. (A and B) ALDH1A1+ cells were located singularly, in groups and more centrally within cell nests. (C) Tumor expressing ALDH1A1 completely. (D-F) CD44, EGFR and Ki-67 were expressed marginally to generally within the cell nests. (G and H) ALDH1A1 expression pattern only partly overlapped with CD44 or EGFR. (I) The rate of Ki-67+ cells was independent from ALDH1A1 expression. Magnification, ×200; hem counterstaining. ALDH1A1, aldehyde dehydrogenase 1 family, member A1; CD44, hyaluronan receptor cluster of differentiation 44; EGFR, epidermal growth factor receptor; hem, hematoxylin.
Figure 2.
Figure 2.
Survival rates of patients with ALDH1A1+ or ALDH1A1− tumors with known day of mortality. Patients with ALDH1A1+ tumors appeared to exhibit reduced survival. (HPV was an independent prognostic factor for better survival). ALDH1A1, aldehyde dehydrogenase 1 family, member A1; CD44, hyaluronan receptor cluster of differentiation 44; HPV, human papilloma virus.
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References

    1. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11:9–22. doi: 10.1038/nrc2982. - DOI - PubMed
    1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012, cancer incidence and mortality worldwide: IARC cancerbase No. 11 [Internet] 1.0. Lyon, France: IARC; 2013.
    1. Wu MJ, Jan CI, Tsay YG, Yu YH, Huang CY, Lin SC, Liu CJ, Chen YS, Lo JF, Yu CC. Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling. Mol Cancer. 2010;9:283. doi: 10.1186/1476-4598-9-283. - DOI - PMC - PubMed
    1. Chen YC, Chen YW, Hsu HS, Tseng LM, Huang PI, Lu KH, Chen DT, Tai LK, Yung MC, Chang SC, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385:307–313. doi: 10.1016/j.bbrc.2009.05.048. - DOI - PubMed
    1. Clay MR, Tabor M, Owen JH, Carey TE, Bradford CR, Wolf GT, Wicha MS, Prince ME. Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck. 2010;32:1195–1201. doi: 10.1002/hed.21315. - DOI - PMC - PubMed

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