Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26

Nishikawa,Shimpei; Konno,Masamitsu; Hamabe,Atsushi; Hasegawa,Shinichiro; Kano,Yoshihiro; Fukusumi,Takahito; Satoh,Taroh; Takiguchi,Shuji; Mori,Masaki; Doki,Yuichiro; Ishii,Hideshi

doi:10.3892/ol.2015.3063

Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26

Authors:
- Shimpei Nishikawa
- Masamitsu Konno
- Atsushi Hamabe
- Shinichiro Hasegawa
- Yoshihiro Kano
- Takahito Fukusumi
- Taroh Satoh
- Shuji Takiguchi
- Masaki Mori
- Yuichiro Doki
- Hideshi Ishii
View Affiliations

Affiliations: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Otorhinolaryngology‑Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565‑0871, Japan
Published online on: March 20, 2015 https://doi.org/10.3892/ol.2015.3063
Pages: 2361-2367

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

Cancer tissue is maintained by relatively small populations of cancer stem cells (CSCs), which are involved in chemotherapy resistance, recurrence and metastasis. As tumor tissues are comprised of various cells, studies of human clinical samples are important for the characterization of CSCs. In the present study, an expression profiling study was performed in which an anti‑cell surface marker antibody‑based array platform, a flow cytometry‑based cell separation technique and a tumorigenicity analysis in immunodeficient animals were utilized. These approaches revealed that the markers cluster of differentiation (CD)44 and CD26 facilitated the fractionation of surgically resected human gastric cancer (GC) cells into the following subset populations with distinct tumorigenic potentials: Highly tumorigenic CD26+CD44+ cells (6/6 mice formed tumors), moderately tumorigenic CD26+CD44‑ cells (5/6 mice formed tumors), and weakly or non‑tumorigenic CD26‑CD44‑ cells (2/6 mice formed tumors). Furthermore, exposure to 5‑fluorouracil significantly increased the proportion of CD26+ cells in vitro. The present study demonstrated that the combined expression of CD26 and CD44 presents a potential marker of human GC stem cells.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
2	Bang YJ, Van Cutsem E, Feyereislova A, et al: ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar : PubMed/NCBI
3	Lapidot T, Sirard C, Vormoor J, et al: A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature. 367:645–648. 1994. View Article : Google Scholar : PubMed/NCBI
4	Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI
5	Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI
6	Singh SK, Hawkins C, Clarke ID, et al: Identification of human brain tumor initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI
7	O'Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumor growth in immunodeficient mice. Nature. 445:106–110. 2007. View Article : Google Scholar : PubMed/NCBI
8	Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI
9	Li C, Heidt DG, Dalerba P, et al: Identification of pancreatic cancer stem cells. Cancer Res. 67:1030–1037. 2007. View Article : Google Scholar : PubMed/NCBI
10	Haraguchi N, Ishii H, Mimori K, et al: CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest. 120:3326–3339. 2010. View Article : Google Scholar : PubMed/NCBI
11	Takaishi S, Okumura T, Tu S, et al: Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 27:1006–1020. 2009. View Article : Google Scholar : PubMed/NCBI
12	Clarke MF, Dick JE, Dirks PB, et al: Cancer stem cells - perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66:9339–9344. 2006. View Article : Google Scholar : PubMed/NCBI
13	O'Brien CA, Kreso A and Jamieson CH: Cancer stem cells and self-renewal. Clin Cancer Res. 16:3113–3120. 2010. View Article : Google Scholar : PubMed/NCBI
14	Medema JP: Cancer stem cells: the challenges ahead. Nat Cell Biol. 15:338–344. 2013. View Article : Google Scholar : PubMed/NCBI
15	Fukuda K, Saikawa Y, Ohashi M, et al: Tumor initiating potential of side population cells in human gastric cancer. Int J Oncol. 34:1201–1207. 2009.PubMed/NCBI
16	Han ME, Jeon TY, Hwang SH, et al: Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell Mol Life Sci. 68:3589–3605. 2011. View Article : Google Scholar : PubMed/NCBI
17	Zhang C, Li C, He F, Cai Y and Yang H: Identification of CD44⁺CD24⁺ gastric cancer stem cells. J Cancer Res Clin Oncol. 137:1679–1686. 2011. View Article : Google Scholar : PubMed/NCBI
18	Jiang J, Zhang Y, Chuai S, et al: Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene. 31:671–682. 2012. View Article : Google Scholar : PubMed/NCBI
19	Katsuno Y, Ehata S, Yashiro M, Yanagihara K, Hirakawa K and Miyazono K: Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-β. J Pathol. 228:391–404. 2012. View Article : Google Scholar : PubMed/NCBI
20	Nishikawa S, Konno M, Hamabe A, et al: Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy. Int J Oncol. 42:1437–1442. 2013.PubMed/NCBI
21	Rocco A, Liguori E, Pirozzi G, et al: CD133 and CD44 cell surface markers do not identify cancer stem cells in primary human gastric tumors. J Cell Physiol. 227:2686–2693. 2012. View Article : Google Scholar : PubMed/NCBI
22	Ponti D, Costa A, Zaffaroni N, et al: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI
23	Zola H: Medical applications of leukocyte surface molecules - the CD molecules. Mol Med. 12:312–316. 2006.PubMed/NCBI
24	da Cunha JP, Galante PA, de Souza JE, et al: Bioinformatics construction of the human cell surfaceome. Proc Natl Acad Sci USA. 106:16752–16757. 2009. View Article : Google Scholar : PubMed/NCBI
25	Kreso A, O'Brien CA, van Galen P, et al: Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 339:543–548. 2013. View Article : Google Scholar : PubMed/NCBI
26	Dieter SM, Ball CR, Hoffmann CM, et al: Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell. 9:357–365. 2011. View Article : Google Scholar : PubMed/NCBI