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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Research

Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

Authors: Chun-Yan Li, Bao-Xiu Li, Yi Liang, Rui-Qing Peng, Ya Ding, Da-Zhi Xu, Xin Zhang, Zhi-Zhong Pan, De-Sen Wan, Yi-Xin Zeng, Xiao-Feng Zhu, Xiao-Shi Zhang

Published in: Journal of Translational Medicine | Issue 1/2009

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Abstract

Background

Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors.

Patients and methods

Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed.

Results

The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5%) were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%). Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth.

Conclusion

The fact that a higher percentage CD133+ cells were strongly associated with a poorer prognosis in patients with locally advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor progression, and the overpopulation hypothesis of cancer stem cell seems reasonable.
Appendix
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Literature
1.
Meyerhardt JA, Mayer RJ: Systemic therapy for colorectal cancer. N Engl J Med. 2005, 352 (5): 476-487. 10.1056/NEJMra040958.CrossRefPubMed
2.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58 (2): 71-96. 10.3322/CA.2007.0010.CrossRefPubMed
3.
Omura K: Advances in chemotherapy against advanced or metastatic colorectal cancer. Digestion. 2008, 77 (Suppl 1): 13-22. 10.1159/000111483.CrossRefPubMed
4.
Hecht JR: Current and emerging therapies for metastatic colorectal cancer: applying research findings to clinical practice. Am J Health Syst Pharm. 2008, 65 (11 Suppl 4): S15-21. 10.2146/ajhp080102.CrossRefPubMed
5.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003, 100 (7): 3983-3988. 10.1073/pnas.0530291100.PubMedCentralCrossRefPubMed
6.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB: Identification of human brain tumour initiating cells. Nature. 2004, 432 (7015): 396-401. 10.1038/nature03128.CrossRefPubMed
7.
Boman BM, Wicha MS: Cancer stem cells: a step toward the cure. J Clin Oncol. 2008, 26 (17): 2795-2799. 10.1200/JCO.2008.17.7436.CrossRefPubMed
8.
Wang J, Guo LP, Chen LZ, Zeng YX, Lu SH: Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res. 2007, 67 (8): 3716-3724. 10.1158/0008-5472.CAN-06-4343.CrossRefPubMed
9.
Shmelkov SV, St Clair R, Lyden D, Rafii S: AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005, 37 (4): 715-719. 10.1016/j.biocel.2004.08.010.CrossRefPubMed
10.
Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW: A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997, 90 (12): 5013-5021.PubMed
11.
Yu Y, Flint A, Dvorin EL, Bischoff J: AC133-2, a novel isoform of human AC133 stem cell antigen. J Biol Chem. 2002, 277 (23): 20711-20716. 10.1074/jbc.M202349200.CrossRefPubMed
12.
Bauer N, Fonseca AV, Florek M, Freund D, Jászai J, Bornhäuser M, Fargeas CA, Corbeil D: New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs. 2008, 188 (1–2): 127-138. 10.1159/000112847.CrossRefPubMed
13.
Jászai J, Fargeas CA, Florek M, Huttner WB, Corbeil D: Focus on molecules: prominin-1 (CD133). Exp Eye Res. 2007, 85 (5): 585-586. 10.1016/j.exer.2006.03.022.CrossRefPubMed
14.
Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A, Murphy SK: Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene. 2009, 28 (2): 209-218. 10.1038/onc.2008.374.CrossRefPubMed
15.
Tabu K, Sasai K, Kimura T, Wang L, Aoyanagi E, Kohsaka S, Tanino M, Nishihara H, Tanaka S: Promoter hypomethylation regulates CD133 expression in human gliomas. Cell Res. 2008, 18 (10): 1037-1046. 10.1038/cr.2008.270.CrossRefPubMed
16.
Ruau D, Ensenat-Waser R, Dinger TC, Vallabhapurapu DS, Rolletschek A, Hacker C, Hieronymus T, Wobus AM, Müller AM, Zenke M: Pluripotency associated genes are reactivated by chromatin-modifying agents in neurosphere cells. Stem Cells. 2008, 26 (4): 920-926. 10.1634/stemcells.2007-0649.CrossRefPubMed
17.
Hamdbarzumyan D, Becher OJ, Holland EC: Cancer stem cells and survival pathways. Cell Cycle. 2008, 7 (10): 1371-1378.CrossRef
18.
Murat A, Migliavacca E, Janzer RC, Hegi M: Stem Cell-Related "Self-Renewal" Signature and High Epidermal Growth Factor Receptor Expression Associated With Resistance to Concomitant Chemoradiotherapy in Glioblastoma. J Clin Oncol. 2008, 26 (18): 3015-3024. 10.1200/JCO.2007.15.7164.CrossRefPubMed
19.
Hambardzumyan D, Squatrito M, Holland EC: Radiation resistance and stem-like cells in brain tumors. Cancer Cell. 2006, 10 (6): 454-456. 10.1016/j.ccr.2006.11.008.CrossRefPubMed
20.
Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A: HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 2007, 17 (2): 165-172. 10.1016/j.cub.2006.11.033.PubMedCentralCrossRefPubMed
21.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006, 444 (7120): 756-760. 10.1038/nature05236.CrossRefPubMed
22.
Griguer CE, Oliva CR, Gobin E, Marcorelles P, Benos DJ, Lancaster JR, Gillespie GY: CD133 is a marker of bioenergetic stress in human glioma. PLoS ONE. 2008, 3 (11): e3655-10.1371/journal.pone.0003655.PubMedCentralCrossRefPubMed
23.
Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW: AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997, 90 (12): 5002-5012.PubMed
24.
Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L: Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res. 2008, 10 (1): R10-10.1186/bcr1855.PubMedCentralCrossRefPubMed
25.
Fan X, Eberhart CG: Medulloblastoma stem cells. J Clin Onco. 2008, 26 (17): 2821-2827. 10.1200/JCO.2007.15.2264.CrossRef
26.
Monzani E, Facchetti F, Galmozzi E, Corsini E, Benetti A, Cavazzin C, Gritti A, Piccinini A, Porro D, Santinami M, Invernici G, Parati E, Alessandri G, La Porta CA: Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer. 2007, 43 (5): 935-946. 10.1016/j.ejca.2007.01.017.CrossRefPubMed
27.
Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008, 15 (3): 504-514. 10.1038/sj.cdd.4402283.CrossRefPubMed
28.
Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ, Guan XY: Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007, 132 (7): 2542-2556. 10.1053/j.gastro.2007.04.025.CrossRefPubMed
29.
Collins AT, Maitland NJ: Prostate cancer stem cells. Eur J Cancer. 2006, 42 (9): 1213-1218. 10.1016/j.ejca.2006.01.037.CrossRefPubMed
30.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 2007, 445 (7123): 111-115. 10.1038/nature05384.CrossRefPubMed
31.
O'Brien CA, Pollett A, Gallinger S, Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007, 445 (7123): 106-110. 10.1038/nature05372.CrossRefPubMed
32.
Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007, 104 (24): 10158-10163. 10.1073/pnas.0703478104.PubMedCentralCrossRefPubMed
33.
Haraguchi N, Ohkuma M, Sakashita H, Matsuzaki S, Tanaka F, Mimori K, Kamohara Y, Inoue H, Mori M: CD133+CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol. 2008, 15 (10): 2927-2933. 10.1245/s10434-008-0074-0.CrossRefPubMed
34.
Barker N, van Es JH, Kuipers J, Kujala P, Born van den M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H: Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007, 449 (7165): 1003-1007. 10.1038/nature06196.CrossRefPubMed
35.
Boman BM, Wicha MS, Fields JZ, Runquist OA: Symmetric division of cancer stem cells – a key mechanism in tumor growth that should be targeted in future therapeutic approaches. Clin Pharmacol Ther. 2007, 81 (6): 893-898. 10.1038/sj.clpt.6100202.CrossRefPubMed
36.
37.
Boman BM, Fields JZ, Cavanaugh KL, Guetter A, Runquist OA: How dysregulated colonic crypt dynamics cause stem cell overpopulation and initiate colon cancer. Cancer Res. 2008, 68 (9): 3304-3313. 10.1158/0008-5472.CAN-07-2061.CrossRefPubMed
38.
Morrison SJ, Kimble J: Asymmetric and symmetric stem-cell divisions in development and cancer. Nature. 2006, 441 (7097): 1068-1074. 10.1038/nature04956.CrossRefPubMed
39.
Johnston MD, Edwards CM, Bodmer WF, Maini PK, Chapman SJ: Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer. Proc Natl Acad Sci USA. 2007, 104 (10): 4008-4013. 10.1073/pnas.0611179104.PubMedCentralCrossRefPubMed
40.
Horst D, Kriegl L, Engel J, Kirchner T, Jung A: CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer. 2008, 99 (8): 1285-1289. 10.1038/sj.bjc.6604664.PubMedCentralCrossRefPubMed
41.
Kojima M, Ishii G, Atsumi N, Fujii S, Saito N, Ochiai A: Immunohistochemical detection of CD133 expression in colorectal cancer: a clinicopathological study. Cancer Sci. 2008, 99 (8): 1578-1583. 10.1111/j.1349-7006.2008.00849.x.CrossRefPubMed
42.
Maeda S, Shinchi H, Kurahara H, Mataki Y, Maemura K, Sato M, Natsugoe S, Aikou T, Takao S: CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer. Br J Cancer. 2008, 98 (8): 1389-1397. 10.1038/sj.bjc.6604307.PubMedCentralCrossRefPubMed
43.
Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N, Lichter P, Unterberg A, Radlwimmer B, Herold-Mende CC: Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res. 2008, 14 (1): 123-129. 10.1158/1078-0432.CCR-07-0932.CrossRefPubMed
44.
Beier D, Wischhusen J, Dietmaier W, Hau P, Proescholdt M, Brawanski A, Bogdahn U, Beier CP: CD133 expression and cancer stem cells predict prognosis in high-grade oligodendroglial tumors. Brain Pathol. 2008, 18 (3): 370-377. 10.1111/j.1750-3639.2008.00130.x.CrossRefPubMed
45.
Song W, Li H, Tao K, Li R, Song Z, Zhao Q, Zhang F, Dou K: Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 2008, 62 (8): 1212-1218. 10.1111/j.1742-1241.2008.01777.x.CrossRefPubMed
46.
Zhang HZ, Wei YP, Wang M, Wu C, Yang YQ, Chen J, Cao YK: Association of CD133 and endothelin-converting enzyme expressions with prognosis of non-small cell lung carcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2007, 27 (5): 696-9. [Article in Chinese]PubMed
47.
Jaksch M, Múnera J, Bajpai R, Terskikh A, Oshima RG: Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines. Cancer Res. 2008, 68 (19): 7882-7886. 10.1158/0008-5472.CAN-08-0723.PubMedCentralCrossRefPubMed
48.
Rubio CA: Arrest of cell proliferation in budding tumor cells ahead of the invading edge of colonic carcinomas. A preliminary report. Anticancer Res. 2008, 28 (4C): 2417-2420.PubMed
49.
Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ: Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature. 2009, 457 (7229): 603-607. 10.1038/nature07589.PubMedCentralCrossRefPubMed
50.
Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D'Angelica M, Kemeny N, Lyden D, Rafii S: CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest. 2008, 118 (6): 2111-2120.PubMedCentralPubMed
51.
Lardon J, Corbeil D, Huttner WB, Ling Z, Bouwens L: Stem cell marker prominin-1/AC133 is expressed in duct cells of the adult human pancreas. Pancreas. 2008, 36 (1): e1-6. 10.1097/mpa.0b013e318149f2dc.CrossRefPubMed
52.
Florek M, Haase M, Marzesco AM, Freund D, Ehninger G, Huttner WB, Corbeil D: Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. Cell Tissue Res. 2005, 319 (1): 15-26. 10.1007/s00441-004-1018-z.CrossRefPubMed
53.
Chu P, Clanton DJ, Snipas TS, Lee J, Mitchell E, Nguyen ML, Hare E, Peach RJ: Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer. 2009, 124 (6): 1312-1321. 10.1002/ijc.24061.CrossRefPubMed
54.
Lobo NA, Shimono Y, Qian D, Clarke MF: The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007, 23: 675-699. 10.1146/annurev.cellbio.22.010305.104154.CrossRefPubMed
55.
Merlo LM, Pepper JW, Reid BJ, Maley CC: Cancer as an evolutionary and ecological process. Nat Rev Cancer. 2006, 6 (12): 924-935. 10.1038/nrc2013.CrossRefPubMed
56.
Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, Morrison SJ: Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006, 441 (7092): 475-482. 10.1038/nature04703.CrossRefPubMed
57.
Yilmaz OH, Morrison SJ: The PI-3kinase pathway in hematopoietic stem cells and leukemia-initiating cells: a mechanistic difference between normal and cancer stem cells. Blood Cells Mol Dis. 2008, 41 (1): 73-76. 10.1016/j.bcmd.2008.02.004.PubMedCentralCrossRefPubMed
58.
Willis ND, Przyborski SA, Hutchison CJ, Wilson RG: Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers. J Anat. 2008, 213 (1): 59-65. 10.1111/j.1469-7580.2008.00917.x.PubMedCentralCrossRefPubMed
59.
Shibata D: Stem cells as common ancestors in a colorectal cancer ancestral tree. Curr Opin Gastroenterol. 2008, 24 (1): 59-63. 10.1097/MOG.0b013e3282f2a2e9.CrossRefPubMed
60.
Zou GM: Cancer initiating cells or cancer stem cells in the gastrointestinal tract and liver. J Cell Physiol. 2008, 217 (3): 5q98-604. 10.1002/jcp.21541.CrossRef
Metadata
Title
Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB
Authors
Chun-Yan Li
Bao-Xiu Li
Yi Liang
Rui-Qing Peng
Ya Ding
Da-Zhi Xu
Xin Zhang
Zhi-Zhong Pan
De-Sen Wan
Yi-Xin Zeng
Xiao-Feng Zhu
Xiao-Shi Zhang
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-56

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