Abstract
The concept of cancer stem cell has developed in leukemia. Recently, it has expanded to include solid tumors such as brain or breast tumors. However, the descriptions are not recognized in human gastrointestinal cancers. We used flow cytometry and the DNA-binding dye (Hoechst 33342) to isolate side population (SP) cells from various human gastrointestinal system cancer cell lines. The SP cell fraction is considered to contain abundant stem cells. Fifteen of 16 cancer cell lines from the gastrointestinal system contained 0.3–2.2% SP cells. We studied the characteristics of the SP cells in hepatic or colon cancer cell lines. The results demonstrated that cancers of the gastrointestinal system do contain SP cells that show some characters of so-called stem cells. In this paper, we report our study results with a review of the literature.
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References
Reya T, Morrison SJ, Clarke MF et al. Stem cell, cancer, and cancer stem cell. Nature 2001; 414: 105–11.
Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nature Rev Cancer 2003; 3: 895–902.
Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature 2004; 432: 324–31.
Wulf GG, Wang RY, Kuehnle I et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001; 98: 1166–73.
Lapidot T, Sirard C, Vormoor J et al. A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature 1994; 367: 645–8.
Bonnet D, Dick JE. Human acute leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med 1997; 3: 730–7.
Al-Hajj M, Wicha MS, Benito-Hernandez A et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100: 3983–8.
Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 2004; 101: 781–6.
Hirschmann-Jax C, Foster AE, Wulf GG et al. A distinct ‘side population’ of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 2004; 101: 14228–33.
Hemmati HD, Nakano I, Lazareff JA et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003; 100: 15178–83.
Yuan X, Curtin J, Xiong Y et al. Isolation of cancer stem cells from adult glioblastoma multiform. Oncogene 2004; 23: 9392–400.
Singh SK, Hawkins C, Clarke ID et al. Identification of human brain tumour initiating cells. Nature 2004; 432: 396–401.
Goodell MA, Rosenzweig M, Kim H et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nature Med 1997; 3: 1337–45.
Duxbury MS, Ito H, Zinner MJ et al. CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells. Oncogene 2004; 23: 465–73.
Duxbury MS, Ito H, Benoit E et al. A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells. Cancer Res 2004; 64: 3987–93.
Kakiuchi S, Daigo Y, Ishikawa N et al. Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum. Mol. Genet 2004; 13: 3029–43.
Morrisey EE, Tang Z, Sigrist K et al. GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes Dev 1998; 12: 3579–90.
Plescia C, Rogler C, Rogler L. Genomic expression analysis implicates Wnt signaling pathway and extracellular matrix alterations in hepatic specification and differentiation of murine hepatic stem cells. Differentiation 2001; 68: 254–69.
Zhao R, Watt AJ, Li J et al. GATA6 is essential for embryonic development of the liver but dispensable for early heart formation. Mol Cell Biol 2005; 25: 2622–31.
Nemer G, Nemer M. Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol 2003; 254: 131–48.
Paling NR, Wheadon H, Bone HK et al. Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling. J Biol Chem 2004; 279: 48063–70.
Hu L, Lau SH, Tzang CH et al. Association of vimentin overexpression and hepatocellular carcinoma metastasis. Oncogene 2004; 23: 298–302.
Haruna Y, Saito K, Spaulding S et al. Identification of bipotential progenitor cells in human liver development. Hepatology 1996; 23: 476–81.
Parent R, Marion MJ, Furio L et al. Origin and characterization of a human bipotent liver progenitor cell line. Gastroenterology 2004; 126: 1147–56.
Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005: 275–84. Review.
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Haraguchi, N., Inoue, H., Tanaka, F. et al. Cancer stem cells in human gastrointestinal cancers. Hum Cell 19, 24–29 (2006). https://doi.org/10.1111/j.1749-0774.2005.00004.x
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DOI: https://doi.org/10.1111/j.1749-0774.2005.00004.x