Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas

Wu,Jean; Mu,Qingshan; Thiviyanathan,Varatharasa; Annapragada,Ananth; Vigneswaran,Nadarajah

doi:10.3892/ijo.2014.2677

Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas

Authors:
- Jean Wu
- Qingshan Mu
- Varatharasa Thiviyanathan
- Ananth Annapragada
- Nadarajah Vigneswaran
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Affiliations: Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, TX 77054, USA, Department of Nanomedicine and Biomedical Engineering, The University of Texas Medical School at Houston, Houston, TX 77030, USA, The Singleton Department of Pediatric Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA
Published online on: September 26, 2014 https://doi.org/10.3892/ijo.2014.2677
Pages: 2365-2372

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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.

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1	Levitus M, Joenje H and de Winter JP: The Fanconi anemia pathway of genomic maintenance. Cell Oncol. 28:3–29. 2006.PubMed/NCBI
2	Kutler DI, Singh B, Satagopan J, et al: A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood. 101:1249–1256. 2003.PubMed/NCBI
3	Scheckenbach K, Wagenmann M, Freund M, Schipper J and Hanenberg H: Squamous cell carcinomas of the head and neck in Fanconi anemia: risk, prevention, therapy, and the need for guidelines. Klin Padiatr. 224:132–138. 2012. View Article : Google Scholar : PubMed/NCBI
4	Kutler DI, Auerbach AD, Satagopan J, et al: High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch Otolaryngol Head Neck Surg. 129:106–112. 2003. View Article : Google Scholar : PubMed/NCBI
5	Masserot C, Peffault de Latour R, Rocha V, et al: Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after hematopoietic stem cell transplantation. Cancer. 113:3315–3322. 2008. View Article : Google Scholar : PubMed/NCBI
6	Rosenberg PS, Socié G, Alter BP and Gluckman E: Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood. 105:67–73. 2005. View Article : Google Scholar : PubMed/NCBI
7	Birkeland AC, Auerbach AD, Sanborn E, et al: Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 137:930–934. 2011. View Article : Google Scholar : PubMed/NCBI
8	Kutler DI, Wreesmann VB, Goberdhan A, et al: Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst. 95:1718–1721. 2003. View Article : Google Scholar : PubMed/NCBI
9	Alter BP, Giri N, Savage SA, Quint WG, de Koning MN and Schiffman M: Squamous cell carcinomas in patients with Fanconi anemia and dyskeratosis congenita: a search for human papillomavirus. Int J Cancer. 133:1513–1515. 2013. View Article : Google Scholar : PubMed/NCBI
10	van Zeeburg HJ, Snijders PJ, Pals G, et al: Generation and molecular characterization of head and neck squamous cell lines of fanconi anemia patients. Cancer Res. 65:1271–1276. 2005.PubMed/NCBI
11	Schlacher K, Wu H and Jasin M: A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell. 22:106–116. 2012. View Article : Google Scholar : PubMed/NCBI
12	Gammon L, Biddle A, Fazil B, Harper L and Mackenzie IC: Stem cell characteristics of cell sub-populations in cell lines derived from head and neck cancers of Fanconi anemia patients. J Oral Pathol Med. 40:143–152. 2011. View Article : Google Scholar : PubMed/NCBI
13	Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI
14	Alison MR, Islam S and Wright NA: Stem cells in cancer: instigators and propagators? J Cell Sci. 123:2357–2368. 2010. View Article : Google Scholar : PubMed/NCBI
15	Beck B and Blanpain C: Unravelling cancer stem cell potential. Nat Rev Cancer. 13:727–738. 2013. View Article : Google Scholar : PubMed/NCBI
16	Frank NY, Schatton T and Frank MH: The therapeutic promise of the cancer stem cell concept. J Clin Invest. 120:41–50. 2010. View Article : Google Scholar : PubMed/NCBI
17	Sampieri K and Fodde R: Cancer stem cells and metastasis. Semin Cancer Biol. 22:187–193. 2012. View Article : Google Scholar
18	Noto Z, Yoshida T, Okabe M, et al: CD44 and SSEA-4 positive cells in an oral cancer cell line HSC-4 possess cancer stem-like cell characteristics. Oral Oncol. 49:787–795. 2013. View Article : Google Scholar : PubMed/NCBI
19	Prince ME, Sivanandan R, Kaczorowski A, et al: 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
20	Clay MR, Tabor M, Owen JH, et al: Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck. 32:1195–1201. 2010. View Article : Google Scholar : PubMed/NCBI
21	Marcato P, Dean CA, Giacomantonio CA and Lee PW: Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle. 10:1378–1384. 2011. View Article : Google Scholar : PubMed/NCBI
22	Deng S, Yang X, Lassus H, et al: Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One. 5:e102772010. View Article : Google Scholar : PubMed/NCBI
23	Kim MP, Fleming JB, Wang H, et al: ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma. PLoS One. 6:e206362011. View Article : Google Scholar : PubMed/NCBI
24	Landen CN Jr, Goodman B, Katre AA, et al: Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther. 9:3186–3199. 2010. View Article : Google Scholar : PubMed/NCBI
25	Brenner JC, Graham MP, Kumar B, et al: Genotyping of 73 UM-SCC head and neck squamous cell carcinoma cell lines. Head Neck. 32:417–426. 2010.PubMed/NCBI
26	Loh YH, Wu Q, Chew JL, et al: The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet. 38:431–440. 2006. View Article : Google Scholar : PubMed/NCBI
27	Zhao W, Ji X, Zhang F, Li L and Ma L: Embryonic stem cell markers. Molecules. 17:6196–6236. 2012. View Article : Google Scholar : PubMed/NCBI
28	Clevers H: The cancer stem cell: premises, promises and challenges. Nat Med. 17:313–319. 2011. View Article : Google Scholar : PubMed/NCBI
29	Ponti D, Costa A, Zaffaroni N, et al: 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
30	Zhang S, Balch C, Chan MW, et al: Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 68:4311–4320. 2008. View Article : Google Scholar : PubMed/NCBI
31	Charafe-Jauffret E, Ginestier C, Iovino F, et al: Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res. 16:45–55. 2010. View Article : Google Scholar : PubMed/NCBI
32	Jiang F, Qiu Q, Khanna A, et al: 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
33	Li T, Su Y, Mei Y, et al: ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients’ outcome. Lab Invest. 90:234–244. 2010.PubMed/NCBI
34	Ha PK and Califano JA: The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med. 14:363–369. 2003. View Article : Google Scholar : PubMed/NCBI
35	Ha PK, Chang SS, Glazer CA, Califano JA and Sidransky D: Molecular techniques and genetic alterations in head and neck cancer. Oral Oncol. 45:335–339. 2009. View Article : Google Scholar : PubMed/NCBI
36	Blanpain C, Mohrin M, Sotiropoulou PA and Passegué E: DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell. 8:16–29. 2011. View Article : Google Scholar : PubMed/NCBI
37	Rangwala F, Omenetti A and Diehl AM: Cancer stem cells: repair gone awry? J Oncol. 2011:4653432011. View Article : Google Scholar : PubMed/NCBI
38	Taniguchi T and D’Andrea AD: Molecular pathogenesis of Fanconi anemia: recent progress. Blood. 107:4223–4233. 2006. View Article : Google Scholar : PubMed/NCBI
39	Diehn M, Cho RW and Clarke MF: Therapeutic implications of the cancer stem cell hypothesis. Semin Radiat Oncol. 19:78–86. 2009. View Article : Google Scholar : PubMed/NCBI
40	Ghiaur G, Gerber J and Jones RJ: Concise review: cancer stem cells and minimal residual disease. Stem Cells. 30:89–93. 2012. View Article : Google Scholar : PubMed/NCBI