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Pediatric Surgery International

Published in:

01-01-2011 | Original Article

Isolation and identification of cancer stem cells from a side population of a human hepatoblastoma cell line, HuH-6 clone-5

Authors: Shinichi Hayashi, Keiko Fujita, Sachiko Matsumoto, Masumi Akita, Akira Satomi

Published in: Pediatric Surgery International | Issue 1/2011

Abstract

Purpose

It has been thought that the persistence of even a small number of tumor cells in the body may increase each tumor cell in a similar manner and may allow the disease to proceed. However, only a few percent of such tumor cells exist in cancerous tissue. They are called “cancer stem cells (CSCs)”. If an alternative method of annihilating CSCs is found, it will greatly deter relapse and metastasis. We attempted to identify and separate CSCs in hepatoblastoma aiming to develop a new therapy for hepatoblastoma.

Methods

The side population (SP) method was used as an indicator when extracting the CSC candidate group from the hepatoblastoma cells. The SP cells and non-SP cells were studied for tumourigenesis.

Results

Although tumors were formed when SP fraction cells were inoculated into mice, tumor formation was not observed in non-SP cells. SP cells had higher tumor formation ability compared to non-SP cells.

Conclusion

Cancer stem-like cells were separated by the SP fraction method from hepatoblastoma cells. The in vivo experiment proved that SP fraction cells inoculated into mice were self-replicated, and the existence of cancer stem-like cells was identified.

Lapidot T, Sirard C, Vormoor J et al (1994) A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature 367:645–648CrossRefPubMed

Bao S, Wu O, McLendon RE et al (2006) Glioma stem cells promoter radioresistance by preferential activation of the DNA damage response. Nature 444:756–760CrossRefPubMed

Li L, Neaves WB (2006) Normal stem cells and cancer stem cells: the niche matters. Cancer Res 66:4553–4557CrossRefPubMed

Chiba T, Kita K, Zheng YW et al (2006) Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 44:240–251CrossRefPubMed

Zen Y, Fujii T, Yoshikawa S et al (2007) Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. Am J Pathol 170:1750–1762CrossRefPubMed

Ma S, Chan KW, Hu L et al (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132:2542–2556CrossRefPubMed

Yang ZF, Ho DW, Ng MN et al (2008) Significance of CD90⁺ cancer stem cells in human liver cancer. Cancer Cell 13:153–166CrossRefPubMed

Yang ZF, Ngai P, Ho DW et al (2008) Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 47:919–928CrossRefPubMed

Komuro H, Saihara R, Shinya M et al (2007) Identification of side population cells (stem-like cell population) in pediatric solid tumor cell lines. J Pediatr Surg 42:2040–2045CrossRefPubMed

10.

Morimura T, Fujita K, Akita M, Nagashima M, Satomi A (2008) The proton pump inhibitor inhibits cell growth and induces apoptosis in human hepatoblastoma. Pediatr Surg Int 24:1087–1094CrossRefPubMed

11.

Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737CrossRefPubMed

12.

Al-Hajj M, Wicha MS, Benito-Hernandezs A et al (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988CrossRefPubMed

13.

Ricci-Vitiani L, Lombardi DG, Pilozzi E et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115CrossRefPubMed

14.

Singh SK, Hawkins C, Clark ID et al (2004) Identification of human brain tumor initiating cells. Nature 432:396–401CrossRefPubMed

15.

Clarke MF, Dick JE, Dirks PB et al (2006) Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 66:9339–9344CrossRefPubMed

16.

Kondo T, Setoguchi T, Taga T (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 101:781–786CrossRefPubMed

17.

O’Brien CA, Pollet A, Gallinger S et al (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110CrossRefPubMed

18.

Yin AH, Miraglia S, Zanjani ED et al (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012PubMed

19.

Mizrak D, Brittan M, Alison MR (2008) CD133: molecule of the moment. J Pathol 214:3–9CrossRefPubMed

20.

Yamashita T, Ji J, Budhu A et al (2009) EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 136:1012–1024CrossRefPubMed

21.

Schmelzer E, Zhang L, Bruce A et al (2007) Human hepatic stem cells from fetal and postnatal donors. J Exp Med 204:1973–1987CrossRefPubMed

22.

Yamashita T, Forgues M, Wang W et al (2008) EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 68:1451–1461CrossRefPubMed

23.

Visvader JE, Lindeman G (2008) Cancer stem cells in solid tumors: accumulating evidence and unresolved questions. Cancer 8:755–768PubMed

24.

Das B, Tsuchida R, Baruchel S et al (2009) The idea and evidence for the tumor stemness switch. Regulatory networks in stem cells. Humana Press, New York, pp 473–488

25.

Tsuchida B, Das B, Yeger H et al (2008) Cisplatin treatment increases survival and expansion of a highly tumorigenic side-population fraction by upregulating VEGF/Flt1 autocrine signaling. Oncogene 27:3923–3934CrossRefPubMed

26.

Wu C, Alman BA (2008) Side population cells in human cancers. Cancer Lett 268:1–9CrossRefPubMed

27.

Haraguchi N, Ohkuma M, Sakashita H et al (2008) CD133⁺CD44⁺ Population efficiently enriches colon cancer initiating cells. Ann Surg Oncol 15:2927–2933CrossRefPubMed

Title: Isolation and identification of cancer stem cells from a side population of a human hepatoblastoma cell line, HuH-6 clone-5
Authors: Shinichi Hayashi
Keiko Fujita
Sachiko Matsumoto
Masumi Akita
Akira Satomi
Publication date: 01-01-2011
Publisher: Springer-Verlag
Published in: Pediatric Surgery International / Issue 1/2011
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-010-2719-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Isolation and identification of cancer stem cells from a side population of a human hepatoblastoma cell line, HuH-6 clone-5

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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