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Citations to this article

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors
Sergey V. Shmelkov, … , David Lyden, Shahin Rafii
Sergey V. Shmelkov, … , David Lyden, Shahin Rafii
Published May 22, 2008
Citation Information: J Clin Invest. 2008;118(6):2111-2120. https://doi.org/10.1172/JCI34401.
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Research Article Article has an altmetric score of 13

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

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Abstract

Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133+ tumor cells might give rise to the more aggressive CD133– subset, which is also capable of tumor initiation in NOD/SCID mice.

Authors

Sergey V. Shmelkov, Jason M. Butler, Andrea T. Hooper, Adilia Hormigo, Jared Kushner, Till Milde, Ryan St. Clair, Muhamed Baljevic, Ian White, David K. Jin, Amy Chadburn, Andrew J. Murphy, David M. Valenzuela, Nicholas W. Gale, Gavin Thurston, George D. Yancopoulos, Michael D’Angelica, Nancy Kemeny, David Lyden, Shahin Rafii

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 3 8 11 9 19 13 15 14 19 19 29 32 53 35 49 44 33 14 419
Citation information
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Citations to this article in year 2009 (33)

Title and authors Publication Year
CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice and are regulated by thyrotropin
S Friedman, M Lu, A Schultz, D Thomas, RY Lin
PloS one 2009
Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment
G Bertolini, L Roz, P Perego, M Tortoreto, E Fontanella, L Gatti, G Pratesi, A Fabbri, F Andriani, S Tinelli, E Roz, R Caserini, SL Vullo, T Camerini, L Mariani, D Delia, E Calabrò, U Pastorino, G Sozzi
Proceedings of the National Academy of Sciences 2009
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Crosstalk of Notch with p53 and p63 in cancer growth control
GP Dotto
Nature Reviews Cancer 2009
Loss of the Cholesterol-Binding Protein Prominin-1/CD133 Causes Disk Dysmorphogenesis and Photoreceptor Degeneration
S Zacchigna, H Oh, M Wilsch-Brauninger, E Missol-Kolka, J Jaszai, S Jansen, N Tanimoto, F Tonagel, M Seeliger, WB Huttner, D Corbeil, M Dewerchin, S Vinckier, L Moons, P Carmeliet
The Journal of neuroscience : the official journal of the Society for Neuroscience 2009
Colon cancer stem cells
L Ricci-Vitiani, E Fabrizi, E Palio, RD Maria
Journal of Molecular Medicine 2009
Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells
KS Chan, I Espinosa, M Chao, D Wong, L Ailles, M Diehn, H Gill, J Presti, HY Chang, M de Rijn, L Shortliffe, IL Weissman
Proceedings of the National Academy of Sciences 2009
Melanoma-initiating cells: a compass needed
Y Refaeli, A Bhoumik, DR Roop, ZA Ronai
EMBO reports 2009
High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem/progenitor cells
PE Burger, R Gupta, X Xiong, CS Ontiveros, SN Salm, D Moscatelli, EL Wilson
Stem Cells 2009
Identification of gastric cancer stem cells using the cell surface marker CD44
S Takaishi, T Okumura, S Tu, SS Wang, W Shibata, R Vigneshwaran, SA Gordon, Y Shimada, TC Wang
Stem Cells 2009
The malignant pleural effusion as a model to investigate intratumoral heterogeneity in lung cancer
SK Basak, MS Veena, S Oh, G Huang, E Srivatsan, M Huang, S Sharma, RK Batra
PloS one 2009
Characterisation of normal and cancer stem cells: One experimental paradigm for two kinds of stem cells
JF Mayol, C Loeuillet, F Hérodin, D Wion
BioEssays 2009
Stem cells in gastroenterology and hepatology
M Quante, TC Wang
Nature reviews. Gastroenterology & hepatology 2009
Isolation of tumour stem-like cells from benign tumours
Q Xu, X Yuan, P Tunici, G Liu, X Fan, M Xu, J Hu, JY Hwang, DL Farkas, KL Black, JS Yu
British Journal of Cancer 2009
New Therapeutics Targeting Colon Cancer Stem Cells
A Thenappan, Y Li, K Shetty, L Johnson, EP Reddy, L Mishra
Current Colorectal Cancer Reports 2009
Characterization of CD133+ parenchymal cells in the liver: histology and culture
S Yoshikawa, Y Zen, T Fujii, Y Sato, T Ohta, Y Aoyagi, Y Nakanuma
World journal of gastroenterology : WJG 2009
Glioblastoma formation from cell population depleted of Prominin1-expressing cells
K Nishide, Y Nakatani, H Kiyonari, T Kondo
PloS one 2009
Expression of stem cell markers in the human fetal kidney
S Metsuyanim, O Harari-Steinberg, E Buzhor, D Omer, N Pode-Shakked, H Ben-Hur, R Halperin, D Schneider, B Dekel
PloS one 2009
Tumor biology and cancer therapy - an evolving relationship
T Seufferlein, J Ahn, D Krndija, U Lother, G Adler, G Wichert
Cell communication and signaling : CCS 2009
Newly characterised ex vivo colospheres as a three-dimensional colon cancer cell model of tumour aggressiveness
LB Weiswald, S Richon, P Validire, M Briffod, R Lai-Kuen, FP Cordelières, F Bertrand, D Dargere, G Massonnet, E Marangoni, B Gayet, M Pocard, I Bieche, MF Poupon, D Bellet, V Dangles-Marie
British Journal of Cancer 2009
Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB
CY Li, BX Li, Y Liang, RQ Peng, Y Ding, DZ Xu, X Zhang, ZZ Pan, DS Wan, YX Zeng, XF Zhu, XS Zhang
Journal of Translational Medicine 2009
Number crunching in the cancer stem cell market
MR Alison, S Islam, SM Lim
Breast Cancer Research 2009
Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis
EH Huang, MJ Hynes, T Zhang, C Ginestier, G Dontu, H Appelman, JZ Fields, MS Wicha, BM Boman
Cancer research 2009
Expression of gastrin precursors by CD133-positive colorectal cancer cells is crucial for tumour growth
A Ferrand, MS Sandrin, A Shulkes, GS Baldwin
Biochimica et Biophysica Acta 2009
The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling
L Lin, R Amin, GI Gallicano, E Glasgow, W Jogunoori, JM Jessup, M Zasloff, JL Marshall, K Shetty, L Johnson, L Mishra, AR He
Oncogene 2009
Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion
F Varnat, A Duquet, M Malerba, M Zbinden, C Mas, P Gervaz, AR Altaba
EMBO Molecular Medicine 2009
Cancer stem cells in multiple myeloma
N Ghosh, W Matsui
Cancer Letters 2009
SSEA-1 Is an Enrichment Marker for Tumor-Initiating Cells in Human Glioblastoma
Son MJ, Woolard K, Nam DH, Lee J, Fine HA
Cell Stem Cell 2009
Characterization of human embryonic stem cells with features of neoplastic progression.
Werbowetski-Ogilvie TE, Bossé M, Stewart M, Schnerch A, Ramos-Mejia V, Rouleau A, Wynder T, Smith MJ, Dingwall S, Carter T, Williams C, Harris C, Dolling J, Wynder C, Boreham D, Bhatia M
Nature Biotechnology 2009
Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications.
Ischenko I, Seeliger H, Kleespies A, Angele MK, Eichhorn ME, Jauch KW, Bruns CJ
Langenbeck's Archives of Surgery 2009
Endothelial progenitor cell dysfunction in rheumatic disease.
Westerweel PE, Verhaar MC
Nature reviews. Rheumatology 2009
Stem cells and solid cancers.
McDonald SA, Graham TA, Schier S, Wright NA, Alison MR
Virchows Archiv : an international journal of pathology 2009
Both CD133+ and CD133− subpopulations of A549 and H446 cells contain cancer‐initiating cells
Meng X, Li M, Wang X, Wang Y, Ma D
Cancer Science 2009

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