Abstract
Introduction
Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissue have demonstrated presence of SP cells including different gastric cancer cell lines. However, is that true all SP cells contain cancer stem-like cells in gastric cancer cell lines?
Materials and methods
MKN-45 and BGC-823 cells labeled with Hoechst 33342 were chosen to obtain SP cells, then characterized the cancer stem-like properties of SP cells both in vitro and in vivo. Five stemness–related genes expression profiles, including OCT-4, SOX-2, NANOG, CD44 and ATP-binding cassette transporters gene ABCG-2, were tested in SP and MP cells using quantitative real-time RT-PCR. Western blot was chosen to show the difference of protein expression between SP and MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells from MKN-45 showed higher tumorigenesis tendency than MP cells, but SP cells from BGC-823 showed same tumorgenesis tendency as MP cells.
Conclusion
SP cells from MKN-45 possess cancer stem cell properties and proved that they were gastric cancer stem-like cells. SP cells from BGC-823 didn’t possess cancer stem cell properties and proved that not all SP cells contain cancer stem-like cells in gastric cancer cell lines.
Similar content being viewed by others
References
Reya T, Morrison SJ, Clarke MF, et al. Stem cell, cancer, and cancer stem cell. Nature. 2001;414:105–111.
Houghton JM, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306:1568–1571.
McDonald S, Greaves L, Gutierrez-Gonzalez L, et al. Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Gastroenterology. 2008;134:500–510.
Alvi AJ, Clayton H, Joshi C, et al. Functional and molecular characterisation of mammary side population cells. Breast Cancer Res. 2003;5:R1–R8.
Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–115.
Chiba T, Kita K, Zheng YW, et al. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006;44:240–251.
Jeremy EO, Benjamin RG, Sanjai KA, et al. Hoechst 33342 side population identification is a conserved and unified mechanism in urological cancers. Stem Cell Dev. 2009;18:1515–1522.
Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA. 2006;103:11154–11159.
Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007;67:4827–4833.
Kazumasa F, Yoshiro S, Masaki O, et al., Tumor initiating potential of side population cells in human gastric cancer. Int J Onco. 2009;34:1201–1207.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
Guenter J. Krejs: gastric cancer: epidemiology and risk factors. Dig Dis. 2010;28:600–603.
Goodell MA, Browse K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797–1806.
Dingzhi H, Quanli G, Liping G, et al. Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev. 2009;18:465–471.
Hadnagy A, Gaboury L, Beaulieu R, Balickia D. SP analysis may be used to identify cancer stem cell populations. Exp Cell Res. 2006;312:3701–3710.
Li H, Hamou MF, de Tribolet N, et al. Variant CD44 adhesion molecules are expressed in human brain metastases but not in glioblastomas. Cancer Res. 1993;53:5345–5349.
Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–3988.
Zhang C, Li C, He F, Cai Y, Yang H. Identification of CD44 + CD24 + gastric cancer stem cells. J Cancer Res Clin Oncol. 2011;137:1679–1686.
Song Z, Yue W, Wei B, et al. Sonic hedgehog pathway is essential for maintenance of cancer stem-like cells in human gastric cancer. PLoS One. 2011;6:e17687.
Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature. 2006;441:1068–1074.
Naotsugu H, Tohru U, Hiroshi I, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 2006;24:506–513.
Boiani M, Scholer HR, Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005;6:872–884.
Chambers I, Colby D, Robertson M, et al. Functional expression cloning of NANOG, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113:643–655.
Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122:947–956.
Zhou S, Schuetz JD, Bunting KD, et al. 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. 2001;7:1028–1034.
Takaishi S, Okumura T, Tu S, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009;27:1006–1022.
Leung EL, Fiscus RR, Tung JW. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 2010;5:e14062.
Acknowledgments
The authors thank Junying Jia and Chunchun Liu (Bio-physics Institute of Chinese Academy) for the help in cell sorting. This study was supported by grants from National Natural Science Fund (81172368).
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Haihong Zhang and Hongqing Xi contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Zhang, H., Xi, H., Cai, A. et al. Not All Side Population Cells Contain Cancer Stem-Like Cells in Human Gastric Cancer Cell Lines. Dig Dis Sci 58, 132–139 (2013). https://doi.org/10.1007/s10620-012-2330-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-012-2330-1