Full Text:   <2911>

CLC number: R73-3

On-line Access: 2011-12-30

Received: 2011-05-12

Revision Accepted: 2011-10-27

Crosschecked: 2011-12-14

Cited: 8

Clicked: 6487

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2012 Vol.13 No.1 P.11-19

http://doi.org/10.1631/jzus.B1100154


Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells


Author(s):  Zhong Shi, Rui Bai, Zhi-xuan Fu, Yong-liang Zhu, Rong-fu Wang, Shu Zheng

Affiliation(s):  Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Zhejiang Province, China), the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China, Department of Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China, Center for Cell and Gene Therapy, Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA

Corresponding email(s):   zhengshu@zju.edu.cn

Key Words:  Induced pluripotent stem cell, Cancer stem cell, Colorectal cancer, NANOG, 5-Fluorouracil


Zhong Shi, Rui Bai, Zhi-xuan Fu, Yong-liang Zhu, Rong-fu Wang, Shu Zheng. Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells[J]. Journal of Zhejiang University Science B, 2012, 13(1): 11-19.

@article{title="Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells",
author="Zhong Shi, Rui Bai, Zhi-xuan Fu, Yong-liang Zhu, Rong-fu Wang, Shu Zheng",
journal="Journal of Zhejiang University Science B",
volume="13",
number="1",
pages="11-19",
year="2012",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1100154"
}

%0 Journal Article
%T Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells
%A Zhong Shi
%A Rui Bai
%A Zhi-xuan Fu
%A Yong-liang Zhu
%A Rong-fu Wang
%A Shu Zheng
%J Journal of Zhejiang University SCIENCE B
%V 13
%N 1
%P 11-19
%@ 1673-1581
%D 2012
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1100154

TY - JOUR
T1 - Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells
A1 - Zhong Shi
A1 - Rui Bai
A1 - Zhi-xuan Fu
A1 - Yong-liang Zhu
A1 - Rong-fu Wang
A1 - Shu Zheng
J0 - Journal of Zhejiang University Science B
VL - 13
IS - 1
SP - 11
EP - 19
%@ 1673-1581
Y1 - 2012
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1100154


Abstract: 
Objective: We aimed to perform a preliminary study of the association between induced pluripotent stem cell (iPS)-related genes and biological behavior of human colorectal cancer (CRC) cells, and the potential for developing anti-cancer drugs targeting these genes. Methods: We used real-time reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate the transcript levels of iPS-related genes NANOG, OCT4, SOX2, C-MYC and KLF4 in CRC cell lines and cancer stem cells (CSCs)-enriched tumor spheres. NANOG was knockdowned in CRC cell line SW620 by lentiviral transduction. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, plate colony formation, and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW620 cells. Also, mock-knockdown and NANOG-knockdown cells were treated with 5-Fluorouracil (5-FU) and survival rate was measured by MTT assay to evaluate drug sensitivity. Results: A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was observed. NANOG knockdown suppressed proliferation, colony formation, and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW620 cells. 5-FU treatment greatly inhibited the expression of the major stemness-associated genes NANOG, OCT4, and SOX2. Conclusions: These results collectively suggest an overlap between iPS-related genes and CSCs in CRC. Quenching a certain gene NANOG may truncate the aggressiveness of CRC cells.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Almstrup, K., Hoei-Hansen, C.E., Wirkner, U., Blake, J., Schwager, C., Ansorge, W., Nielsen, J.E., Skakkebaek, N.E., Rajpert-de Meyts, E., Leffers, H., 2004. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res., 64(14):4736-4743.

[2]Bae, K.M., Su, Z., Frye, C., McClellan, S., Allan, R.W., Andrejewski, J.T., Kelley, V., Jorgensen, M., Steindler, D.A., Vieweg, J., et al., 2010. Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells. J. Urol., 183(5):2045-2053.

[3]Ben-Porath, I., Thomson, M.W., Carey, V.J., Ge, R., Bell, G.W., Regev, A., Weinberg, R.A., 2008. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet., 40(5):499-507.

[4]Bjerkvig, R., Tysnes, B.B., Aboody, K.S., Najbauer, J., Terzis, A.J., 2005. Opinion: the origin of the cancer stem cell: current controversies and new insights. Nat. Rev. Cancer, 5(11):899-904.

[5]Cao, L., Zhou, Y., Zhai, B., Liao, J., Xu, W., Zhang, R., Li, J., Zhang, Y., Chen, L., Qian, H., et al., 2011. Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol., 11(1):71.

[6]Carette, J.E., Pruszak, J., Varadarajan, M., Blomen, V.A., Gokhale, S., Camargo, F.D., Wernig, M., Jaenisch, R., Brummelkamp, T.R., 2010. Generation of iPSCs from cultured human malignant cells. Blood, 115(20):4039-4042.

[7]Dallas, N.A., Xia, L., Fan, F., Gray, M.J., Gaur, P., van Buren, G.II, Samuel, S., Kim, M.P., Lim, S.J., Ellis, L.M., 2009. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res., 69(5):1951-1957.

[8]Dontu, G., Abdallah, W.M., Foley, J.M., Jackson, K.W., Clarke, M.F., Kawamura, M.J., Wicha, M.S., 2003. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev., 17(10):1253-1270.

[9]Dylla, S.J., Beviglia, L., Park, I.K., Chartier, C., Raval, J., Ngan, L., Pickell, K., Aguilar, J., Lazetic, S., Smith-Berdan, S., et al., 2008. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One, 3(6):e2428.

[10]Fan, X., Ouyang, N., Teng, H., Yao, H., 2011. Isolation and characterization of spheroid cells from the HT29 colon cancer cell line. Int. J. Colorectal Dis., 26(10):1279-1285.

[11]Fang, X., Yu, W., Li, L., Shao, J., Zhao, N., Chen, Q., Ye, Z., Lin, S.C., Zheng, S., Lin, B., 2010. ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers. OMICS, 14(4):369-384.

[12]Freyer, J.P., Sutherland, R.M., 1980. Selective dissociation and characterization of cells from different regions of multicell tumor spheroids. Cancer Res., 40(11):3956-3965.

[13]Galli, R., Binda, E., Orfanelli, U., Cipelletti, B., Gritti, A., de Vitis, S., Fiocco, R., Foroni, C., Dimeco, F., Vescovi, A., 2004. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res., 64(19):7011-7021.

[14]Jeter, C.R., Badeaux, M., Choy, G., Chandra, D., Patrawala, L., Liu, C., Calhoun-Davis, T., Zaehres, H., Daley, G.Q., Tang, D.G., 2009. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells, 27(5):993-1005.

[15]Kelly, P.N., Dakic, A., Adams, J.M., Nutt, S.L., Strasser, A., 2007. Tumor growth need not be driven by rare cancer stem cells. Science, 317(5836):337.

[16]Korkaya, H., Wicha, M.S., 2010. Cancer stem cells: nature versus nurture. Nat. Cell Biol., 12(5):419-421.

[17]Lacerda, L., Pusztai, L., Woodward, W.A., 2010. The role of tumor initiating cells in drug resistance of breast cancer: implications for future therapeutic approaches. Drug Resist. Updat., 13(4-5):99-108.

[18]Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M.A., Dick, J.E., 1994. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367(6464):645-648.

[19]Li, F., Tiede, B., Massague, J., Kang, Y., 2007. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res., 17(1):3-14.

[20]Ma, S., Tang, K.H., Chan, Y.P., Lee, T.K., Kwan, P.S., Castilho, A., Ng, I., Man, K., Wong, N., To, K.F., et al., 2010. miR-130b Promotes CD133+ liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell, 7(6):694-707.

[21]Meng, H.M., Zheng, P., Wang, X.Y., Liu, C., Sui, H.M., Wu, S.J., Zhou, J., Ding, Y.Q., Li, J.M., 2010. Overexpression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol. Ther., 9(4):295-302.

[22]Miyoshi, N., Ishii, H., Nagai, K., Hoshino, H., Mimori, K., Tanaka, F., Nagano, H., Sekimoto, M., Doki, Y., Mori, M., 2010. Defined factors induce reprogramming of gastrointestinal cancer cells. PNAS, 107(1):40-45.

[23]Morrison, S.J., Kimble, J., 2006. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature, 441(7097):1068-1074.

[24]Park, I.H., Zhao, R., West, J.A., Yabuuchi, A., Huo, H., Ince, T.A., Lerou, P.H., Lensch, M.W., Daley, G.Q., 2008. Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451(7175):141-146.

[25]Quintana, E., Shackleton, M., Sabel, M.S., Fullen, D.R., Johnson, T.M., Morrison, S.J., 2008. Efficient tumour formation by single human melanoma cells. Nature, 456(7222):593-598.

[26]Reya, T., Morrison, S.J., Clarke, M.F., Weissman, I.L., 2001. Stem cells, cancer, and cancer stem cells. Nature, 414(6859):105-111.

[27]Robertson, F.M., Ogasawara, M.A., Ye, Z., Chu, K., Pickei, R., Debeb, B.G., Woodward, W.A., Hittelman, W.N., Cristofanilli, M., Barsky, S.H., 2010. Imaging and analysis of 3D tumor spheroids enriched for a cancer stem cell phenotype. J. Biomol. Screen., 15(7):820-829.

[28]Saigusa, S., Tanaka, K., Toiyama, Y., Yokoe, T., Okugawa, Y., Ioue, Y., Miki, C., Kusunoki, M., 2009. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann. Surg. Oncol., 16(12):3488-3498.

[29]Saiki, Y., Ishimaru, S., Mimori, K., Takatsuno, Y., Nagahara, M., Ishii, H., Yamada, K., Mori, M., 2009. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Ann. Surg. Oncol., 16(9):2638-2644.

[30]Shackleton, M., Quintana, E., Fearon, E.R., Morrison, S.J., 2009. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell, 138(5):822-829.

[31]Sherar, M.D., Noss, M.B., Foster, F.S., 1987. Ultrasound backscatter microscopy images the internal structure of living tumour spheroids. Nature, 330(6147):493-495.

[32]Singh, A., Settleman, J., 2010. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 29(34):4741-4751.

[33]Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., Dirks, P.B., 2004. Identification of human brain tumour initiating cells. Nature, 432(7015):396-401.

[34]Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S., 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5):861-872.

[35]Tang, C., Ang, B.T., Pervaiz, S., 2007. Cancer stem cell: target for anti-cancer therapy. FASEB J., 21(14):3777-3785.

[36]Tindall, M.J., Please, C.P., 2007. Modelling the cell cycle and cell movement in multicellular tumour spheroids. Bull. Math. Biol., 69(4):1147-1165.

[37]Todaro, M., Alea, M.P., di Stefano, A.B., Cammareri, P., Vermeulen, L., Iovino, F., Tripodo, C., Russo, A., Gulotta, G., Medema, J.P., et al., 2007. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell, 1(4):389-402.

[38]Waleh, N.S., Brody, M.D., Knapp, M.A., Mendonca, H.L., Lord, E.M., Koch, C.J., Laderoute, K.R., Sutherland, R.M., 1995. Mapping of the vascular endothelial growth factor-producing hypoxic cells in multicellular tumor spheroids using a hypoxia-specific marker. Cancer Res., 55(24):6222-6226.

[39]Wang, X., Kruithof-de Julio, M., Economides, K.D., Walker, D., Yu, H., Halili, M.V., Hu, Y.P., Price, S.M., Abate-Shen, C., Shen, M.M., 2009. A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature, 461(7263):495-500.

[40]Wei, D., Kanai, M., Huang, S., Xie, K., 2006. Emerging role of KLF4 in human gastrointestinal cancer. Carcinogenesis, 27(1):23-31.

[41]Wibe, E., 1980. Resistance to vincristine of human cells grown as multicellular spheroids. Br. J. Cancer, 42(6):937-941.

[42]Yeung, T.M., Gandhi, S.C., Wilding, J.L., Muschel, R., Bodmer, W.F., 2010. Cancer stem cells from colorectal cancer-derived cell lines. PNAS, 107(8):3722-3727.

[43]Yin, B.B., Wu, S.J., Zong, H.J., Ma, B.J., Cai, D., 2011. Preliminary screening and identification of stem cell-like sphere clones in a gallbladder cancer cell line GBC-SD. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 12(4):256-263.

[44]Yori, J.L., Johnson, E., Zhou, G., Jain, M.K., Keri, R.A., 2010. Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression. J. Biol. Chem., 285(22):16854-16863.

[45]Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., et al., 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858):1917-1920.

[46]Zhao, W., Hisamuddin, I.M., Nandan, M.O., Babbin, B.A., Lamb, N.E., Yang, V.W., 2004. Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer. Oncogene, 23(2):395-402.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE