Top

Gastric Cancer

Published in:

01-10-2012 | Original article

Expressions of putative cancer stem cell markers ABCB1, ABCG2, and CD133 are correlated with the degree of differentiation of gastric cancer

Authors: Yang Jiang, Yan He, Hui Li, Hui-Ning Li, Lei Zhang, Wei Hu, Ya-Meng Sun, Fu-Lai Chen, Xiao-Ming Jin

Published in: Gastric Cancer | Issue 4/2012

Abstract

Background

The present study was carried out to determine whether a quantitative relationship exists between the expressions of 3 cancer stem cell (CSC) markers and the degree of differentiation of gastric cancer.

Methods

The expressions of 3 putative CSC markers, ABCB1, ABCG2, and CD133, were detected in 90 human gastric adenocarcinoma cases by immunofluorescence assay. The differentiation statuses of 3 gastric cancer cell lines (the undifferentiated gastric cancer cell line HGC-27, the poorly differentiated gastric cancer cell line BGC-823, and the moderately-poorly differentiated gastric adenocarcinoma cell line SGC-7901) were observed and compared by performing the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Gastric xenotransplant cancers in nude mice were constructed to compare the malignancy of the 3 variously differentiated gastric cancer cell lines. The expressions of the 3 putative CSC markers were also detected in the 3 gastric cancer cell lines in vitro by flow cytometric analysis and in the 3 gastric xenotransplant cancers in vivo by immunofluorescence staining.

Results

The expressions of ABCB1, ABCG2, and CD133 were generally correlated with the degree of differentiation of the gastric cancers. In the human gastric adenocarcinomas and in the cancer cell lines, the expressions of ABCB1, ABCG2, and CD133 increased with the increases in the malignancy grades of the gastric cancers. In the human gastric adenocarcinomas, poorly differentiated adenocarcinoma expressed more ABCB1, ABCG2, and CD133 than well-differentiated adenocarcinoma. In addition, the expressions of ABCB1 and CD133 were higher in the diffuse type than in the intestinal type of human gastric cancers. The undifferentiated cell line HGC-27 expressed more putative CSC markers than the moderately-poorly differentiated cell line SGC-7901. Similar results were observed in the xenotransplant tumors that arose from the 3 gastric cancer cell lines.

Conclusions

The expressions of the CSC markers ABCB1, ABCG2, and CD133 differed in the gastric cancers with various degrees of differentiation, with poorly differentiated gastric cancer expressing relatively more CSC markers.

Available only for authorised users

Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004;23:7274–82.PubMedCrossRef

Ricci-Vitiani L, Pagliuca A, Palio E, Zeuner A, De Maria R. Colon cancer stem cells. Gut. 2008;57:538–48.PubMedCrossRef

Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.PubMedCrossRef

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.PubMedCrossRef

Natarajan TG, FitzGerald KT. Markers in normal and cancer stem cells. Cancer Biomark. 2007;3:211–31.PubMed

Mimeault M, Hauke R, Mehta PP, Batra SK. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med. 2007;11:981–1011.PubMedCrossRef

Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 2nd Ed. Gastric Cancer. 1998; 1:10–24.

He Y, Jiang Y, Li YJ, Liu XH, Zhang L, Liu LJ, et al. 19-peptide, a fragment of tumstatin, inhibits the growth of poorly differentiated gastric carcinoma cells in vitro and in vivo. J Gastroenterol Hepatol. 2010;25:935–41.PubMedCrossRef

Surowiak P, Materna V, Matkowski R, Szczuraszek K, Kornafel J, Wojnar A, et al. Relationship between the expression of cyclooxygenase 2 and MDR1/P-glycoprotein in invasive breast cancers and their prognostic significance. Breast Cancer Res. 2005;7:R862–70.PubMedCrossRef

10.

Lazar D, Taban S, Sporea I, Dema A, Cornianu M, Lazar E, et al. Gastric cancer: correlation between clinicopathological factors and survival of patients. II. Rom J Morphol Embryol. 2009;50:185–94.PubMed

11.

Kesler KA, Rieger KM, Ganjoo KN, Sharma M, Fineberg NS, Einhorn LH, et al. Primary mediastinal nonseminomatous germ cell tumors: the influence of postchemotherapy pathology on long-term survival after surgery. J Thorac Cardiovasc Surg. 1999;118:692–700.PubMedCrossRef

12.

Rizo A, Vellenga E, de Haan G, Schuringa JJ. Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum Mol Genet. 2006;2:R210–9.CrossRef

13.

Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2− cancer cells are similarly tumorigenic. Cancer Res. 2005;65:6207–19.PubMedCrossRef

14.

List AF, Kopecky KJ, Willman CL, Head DR, Persons DL, Slovak ML, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2001;98:3212–20.PubMedCrossRef

15.

Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, et al. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 2009;4:226–35.PubMedCrossRef

16.

Zen Y, Fujii T, Yoshikawa S, Takamura H, Tani T, Ohta T, et al. Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. Am J Pathol. 2007;170:1750–62.PubMedCrossRef

17.

Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005;37:715–9.PubMedCrossRef

18.

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMedCrossRef

19.

Beier D, Wischhusen J, Dietmaier W, Hau P, Proescholdt M, Brawanski A, et al. CD133 expression and cancer stem cells predict prognosis in high-grade oligodendroglial tumors. Brain Pathol. 2008;18:370–7.PubMedCrossRef

20.

Ma YH, Mentlein R, Knerlich F, Kruse ML, Mehdorn HM, Held-Feindt J. Expression of stem cell markers in human astrocytomas of different WHO grades. J Neurooncol. 2008;86:31–45.PubMedCrossRef

Title: Expressions of putative cancer stem cell markers ABCB1, ABCG2, and CD133 are correlated with the degree of differentiation of gastric cancer
Authors: Yang Jiang
Yan He
Hui Li
Hui-Ning Li
Lei Zhang
Wei Hu
Ya-Meng Sun
Fu-Lai Chen
Xiao-Ming Jin
Publication date: 01-10-2012
Publisher: Springer Japan
Published in: Gastric Cancer / Issue 4/2012
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI: https://doi.org/10.1007/s10120-012-0140-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2012

Second-line chemotherapy for advanced gastric cancer in Korea

Comparative analysis of the efficacy and safety of chemotherapy with oxaliplatin plus fluorouracil/leucovorin between elderly patients over 65 years and younger patients with advanced gastric cancer

Magnifying endoscopy with narrow-band imaging helps determine the management of gastric adenomas

Efficacy of weekly paclitaxel in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy

Decreased number and reduced NKG2D expression of Vδ1 γδ T cells are involved in the impaired function of Vδ1 γδ T cells in the tissue of gastric cancer

Adenovirus-mediated expression of p33ING1b induces apoptosis and inhibits proliferation in gastric adenocarcinoma cells in vitro

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials