Downregulation of OCT4 promotes differentiation and inhibits growth of BE (2)-C human neuroblastoma I-type cells

Yang,Lin; Zheng,Jicui; Xu,Ting; Xiao,Xianmin

doi:10.3892/or.2013.2356

Downregulation of OCT4 promotes differentiation and inhibits growth of BE (2)-C human neuroblastoma I-type cells

Authors:
- Lin Yang
- Jicui Zheng
- Ting Xu
- Xianmin Xiao
View Affiliations

Affiliations: Department of Surgery, Children's Hospital of Fudan University, Shanghai 201102, P.R. China
Published online on: March 21, 2013 https://doi.org/10.3892/or.2013.2356
Pages: 2191-2196

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

In in vitro continuous culture, N (neuroblastic)-, S (substrate adherent)- and I (intermediate)-type cells were identified in human neuroblastoma (NB), where I-type is recognized as a stem cell type. Octamer-binding protein 4 (OCT4) is a cell marker used to identify the stemness of cells, whose roles in regulating I-type NB cells have yet to be fully elucidated. In the present study, we assessed the differentiation regulation role of OCT4 in BE (2)-C of I-type cells. We demonstrated that downregulation of OCT4 expression in BE (2)-C was associated with reduced cell proliferation and loss of colony formation ability on soft agar, and prompted BE (2)-C cells to differentiate to S-type cells. By contrast, overexpression of OCT4 increased cell proliferation and colony formation ratio, but no obvious differentiation promotion was observed. Furthermore, induced differentiation of BE (2)-C cells to S-type by 5-bromo-2'-deoxyuridine (BrdUrd) was accompanied by reduced expression of OCT4.

View Figures

View References

1	Brodeur GM: Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 3:203–216. 2003. View Article : Google Scholar : PubMed/NCBI
2	Maris JM, Hogarty MD, Bagatell R and Cohn SL: Neuroblastoma. Lancet. 369:2106–2120. 2007. View Article : Google Scholar : PubMed/NCBI
3	Shimada H, Umehara S, Monobe Y, et al: International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children’s Cancer Group. Cancer. 92:2451–2461. 2001.
4	Ross RA, Spengler BA, Domenech C, Porubcin M, Rettig WJ and Biedler JL: Human neuroblastoma I-type cells are malignant neural crest stem cells. Cell Growth Differ. 6:449–456. 1995.PubMed/NCBI
5	Walton JD, Kattan DR, Thomas SK, et al: Characteristics of stem cells from human neuroblastoma cell lines and in tumors. Neoplasia. 6:838–845. 2004. View Article : Google Scholar : PubMed/NCBI
6	Ross RA and Spengler BA: Human neuroblastoma stem cells. Semin Cancer Biol. 17:241–247. 2007. View Article : Google Scholar
7	Babaie Y, Herwig R, Greber B, et al: Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells. 25:500–510. 2007. View Article : Google Scholar : PubMed/NCBI
8	Du Z, Jia D, Liu S, et al: Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia. 57:724–733. 2009. View Article : Google Scholar : PubMed/NCBI
9	Chiou SH, Wang ML, Chou YT, et al: Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 70:10433–10444. 2010. View Article : Google Scholar : PubMed/NCBI
10	Ikushima H, Todo T, Ino Y, et al: Glioma-initiating cells retain their tumorigenicity through integration of the Sox axis and Oct4 protein. J Biol Chem. 286:41434–41441. 2011. View Article : Google Scholar : PubMed/NCBI
11	Liu CG, Lu Y, Wang BB, et al: Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg. 253:1165–1171. 2011. View Article : Google Scholar : PubMed/NCBI
12	Das B, Tsuchida R, Malkin D, Koren G, Baruchel S and Yeger H: Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction. Stem Cells. 26:1818–1830. 2008. View Article : Google Scholar : PubMed/NCBI
13	Melone MA, Giuliano M, Squillaro T, et al: Genes involved in regulation of stem cell properties: studies on their expression in a small cohort of neuroblastoma patients. Cancer Biol Ther. 8:1300–1306. 2009. View Article : Google Scholar : PubMed/NCBI
14	Pietras A, Hansford LM, Johnsson AS, et al: HIF-2alpha maintains an undifferentiated state in neural crest-like human neuroblastoma tumor-initiating cells. Proc Natl Acad Sci USA. 106:16805–16810. 2009. View Article : Google Scholar : PubMed/NCBI
15	Newton TC, Wolcott K and Roberts SS: Comparison of the side populations in pretreatment and postrelapse neuroblastoma cell lines. Transl Oncol. 3:246–251. 2010. View Article : Google Scholar : PubMed/NCBI
16	Nishimura N, Hartomo TB, Pham TV, et al: Epigallocatechin gallate inhibits sphere formation of neuroblastoma BE(2)-C cells. Environ Health Prev Med. 17:246–251. 2012. View Article : Google Scholar : PubMed/NCBI
17	Pezzolo A, Parodi F, Marimpietri D, et al: Oct-4(+)/Tenascin C(+) neuroblastoma cells serve as progenitors of tumor-derived endothelial cells. Cell Res. 21:1470–1486. 2011.
18	Lois C, Hong EJ, Pease S, Brown EJ and Baltimore D: Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science. 295:868–872. 2002. View Article : Google Scholar : PubMed/NCBI
19	Chen YC, Hsu HS, Chen YW, et al: Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One. 3:e26372008. View Article : Google Scholar : PubMed/NCBI
20	Kutner RH, Zhang XY and Reiser J: Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors. Nat Protoc. 4:495–505. 2009. View Article : Google Scholar : PubMed/NCBI
21	Cui H, Ma J, Ding J, Li T, Alam G and Ding HF: Bmi-1 regulates the differentiation and clonogenic self-renewal of I-type neuroblastoma cells in a concentration-dependent manner. J Biol Chem. 281:34696–34704. 2006. View Article : Google Scholar : PubMed/NCBI
22	Marzi I, D’Amico M, Biagiotti T, et al: Purging of the neuroblastoma stem cell compartment and tumor regression on exposure to hypoxia or cytotoxic treatment. Cancer Res. 67:2402–2407. 2007. View Article : Google Scholar : PubMed/NCBI
23	Mahller YY, Williams JP, Baird WH, et al: Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus. PLoS One. 4:e42352009. View Article : Google Scholar : PubMed/NCBI
24	Coulon A, Flahaut M, Muhlethaler-Mottet A, et al: Functional sphere profiling reveals the complexity of neuroblastoma tumor-initiating cell model. Neoplasia. 13:991–1004. 2011.PubMed/NCBI
25	Niwa H: How is pluripotency determined and maintained? Development. 134:635–646. 2007. View Article : Google Scholar : PubMed/NCBI
26	Chiou SH, Yu CC, Huang CY, et al: Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 14:4085–4095. 2008. View Article : Google Scholar : PubMed/NCBI
27	Kim R-J and Nam J-S: OCT4 Expression enhances features of cancer stem cells in a mouse model of breast cancer. Lab Anim Res. 27:147–152. 2011. View Article : Google Scholar : PubMed/NCBI