In vitro and in vivo expression of aldehyde dehydrogenase 1 in oral squamous cell carcinoma

Ota,Nobutaka; Ohno,Jun; Seno,Kei; Taniguchi,Kunihisa; Ozeki,Satoru

doi:10.3892/ijo.2013.2188

In vitro and in vivo expression of aldehyde dehydrogenase 1 in oral squamous cell carcinoma

Authors:
- Nobutaka Ota
- Jun Ohno
- Kei Seno
- Kunihisa Taniguchi
- Satoru Ozeki
View Affiliations

Affiliations: Department of Oral and Maxillofacial Surgery, Division of Oral Oncology, Fukuoka Dental College, Fukuoka 814-0193, Japan, Department of Morphological Biology, Division of Pathology, Fukuoka Dental College, Fukuoka 814-0193, Japan, Department of General Dentistry, Division of General Dentistry, Fukuoka Dental College, Fukuoka 814-0193, Japan
Published online on: November 27, 2013 https://doi.org/10.3892/ijo.2013.2188
Pages: 435-442

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aldehyde dehydrogenase isoform 1 (ALDH1) is a useful marker of cancer-initiating cells (CICs) in various organs. In this study, we investigated whether alterations in ALDH1 immunostaining and enzymatic activity in tumor cell populations predicted clinicopathological factors of prognostic importance for cancer progression and contributed to the characteristics of CICs in cisplatin-treated oral squamous cell cancer (OSCC) cells. We evaluated the association between the proportion of ALDH1-positive tumor cells and the clinicopathological features in 90 patients with OSCC. We also examined ALDH1 enzymatic activity, ABCG2 expression, invasive capacity and the ability to self‑renew in OSCC cells treated with or without cisplatin. The clinicopathological results showed that elevated ALDH1 expression correlated with local recurrence. In in vitro experiments, the percentage of cells exhibiting ALDH1 enzymatic activity significantly increased among cisplatin-surviving cells (CiSCs) according to flow cytometry. Furthermore, CiSCs demonstrated upregulated expression of ABCG2, their invasive capacity increased, and their ability to generate cancer spheres was enhanced. An increased population of cells exhibiting ALDH1 immunostaining is a predictive marker of local recurrence. ALDH1 expression and activity contributes to the characteristics of CICs in OSCC.

View Figures

View References

1.	Al-Hajj M and Clarke MF: Self-renewal and solid tumor stem cells. Oncogene. 23:7274–7282. 2004. View Article : Google Scholar : PubMed/NCBI
2.	Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL and Wahl GM: Cancer stem cells - perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66:9339–9344. 2006. View Article : Google Scholar
3.	Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF and Ailles LE: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 104:973–978. 2007. View Article : Google Scholar : PubMed/NCBI
4.	Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI
5.	Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J and Dirks PB: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI
6.	Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI
7.	Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA and Daidone MG: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI
8.	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
9.	Schwartz GJ, Mehta RH, Wenig BL, Shaligram C and Portugal LG: Salvage treatment for recurrent squamous cell carcinoma of the oral cavity. Head Neck. 22:34–41. 2000. View Article : Google Scholar : PubMed/NCBI
10.	Lindahl R: Aldehyde dehydrogenases and their role in carcinogenesis. Cri Rev Biochem Mol Biol. 27:283–335. 1992. View Article : Google Scholar : PubMed/NCBI
11.	Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS and Dontu G: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 1:555–567. 2007. View Article : Google Scholar : PubMed/NCBI
12.	Ibarra I, Erlich Y, Muthuswamy SK, Sachidanandam R and Hannon GJ: A role for microRNAs in maintenance of mouse mammary epithelial progenitor cells. Genes Dev. 21:3238–3243. 2007. View Article : Google Scholar : PubMed/NCBI
13.	Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, Wang H, Liu Z, Su Y, Stass SA and Katz RL: Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 7:330–338. 2009. View Article : Google Scholar : PubMed/NCBI
14.	Balicki D: Moving forward in human mammary stem cell biology and breast cancer prognostication using ALDH1. Cell Stem Cell. 1:485–487. 2007. View Article : Google Scholar : PubMed/NCBI
15.	Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, Karikari C, Alvarez H, Iacobuzio-Donahue C, Jimeno A, Gabrielson KL, Matsui W and Maitra A: Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 67:2187–2196. 2007. View Article : Google Scholar : PubMed/NCBI
16.	Moreb JS: Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther. 3:237–246. 2008. View Article : Google Scholar : PubMed/NCBI
17.	Rahadiani N, Ikeda J, Mamat S, Matsuzaki S, Ueda Y, Umehara R, Tian T, Wang Y, Enomoto T, Kimura T, et al: Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications. Cancer Sci. 102:903–908. 2011. View Article : Google Scholar : PubMed/NCBI
18.	Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X and Liu J: ALDH1 expression correlates with favorable prognosis in ovarian cancers. Mod Pathol. 22:817–823. 2009.PubMed/NCBI
19.	Marcato P, Dean CA, Pan D, Araslanova R, Gillis M, Joshi M, Helyer L, Pan L, Leidal A, Gujar S, et al: Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform ALDH1A3 and its expression is predictive of metastasis. Stem Cells. 29:32–45. 2011. View Article : Google Scholar : PubMed/NCBI
20.	Gong C, Yao H, Liu Q, Chen J, Shi J, Su F and Song E: Markers of tumor-initiating cells predict chemoresistance in breast cancer. PLoS One. 5:e156302010. View Article : Google Scholar : PubMed/NCBI
21.	Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H and Sorrentino BP: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 7:1028–1034. 2001. View Article : Google Scholar : PubMed/NCBI
22.	Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, Koorstra JB, Rajeshkumar NV, He X, et al: Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst. 102:340–351. 2010. View Article : Google Scholar : PubMed/NCBI
23.	Su Y, Qiu Q, Zhang X, Jiang Z, Leng Q, Liu Z, Stass SA and Jiang F: Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor-initiating cells and associated with progression of bladder cancer. Cancer Epidemiol Biomarkers Prev. 19:327–337. 2010. View Article : Google Scholar : PubMed/NCBI
24.	Li T, Su Y, Mei Y, Leng Q, Leng B, Liu Z, Stass SA and Jiang F: ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Invest. 90:234–244. 2010.PubMed/NCBI
25.	Dave B and Chang J: Treatment resistance in stem cells and breast cancer. J Mammary Gland Biol Neoplasia. 14:79–82. 2009. View Article : Google Scholar : PubMed/NCBI
26.	Lohberger B, Rinner B, Stuendl N, Absenger M, Liegl-Atzwanger B, Walzer SM, Windhager R and Leithner A: Aldehyde dehydrogenase 1, a potential marker for cancer stem cells in human sarcoma. PLoS One. 7:e436642012. View Article : Google Scholar : PubMed/NCBI
27.	Mo W and Zhang JT: Human ABCG2: structure, function, and its role in multidrug resistance. Int J Biochem Mol Biol. 3:1–27. 2012.PubMed/NCBI
28.	Ding XW, Wu JH and Jiang CP: ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy. Life Sci. 86:631–637. 2010. View Article : Google Scholar : PubMed/NCBI
29.	An Y and Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 5:1529–1542. 2009. View Article : Google Scholar : PubMed/NCBI
30.	Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI