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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
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2010 (44)

Title and authors Publication Year
The Therapeutic Promise of the Cancer Stem Cell Concept
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Journal of Clinical Investigation 2010
Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells
L Cui, K Ohuchida, K Mizumoto, T Moriyama, M Onimaru, K Nakata, T Nabae, T Ueki, N Sato, Y Tominaga, M Tanaka
PloS one 2010
Hyaluronan stabilizes focal adhesions, filopodia, and the proliferative phenotype in esophageal squamous carcinoma cells
S Twarock, MI Tammi, RC Savani, JW Fischer
The Journal of biological chemistry 2010
Emerging strategies for the identification and targeting of cancer stem cells
J Dou, N Gu
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Stem cells in hepatocarcinogenesis: evidence from genomic data
JU Marquardt, SS Thorgeirsson
Seminars in liver disease 2010
Molecular genetics of prostate cancer: new prospects for old challenges
MM Shen, C Abate-Shen
Genes & development 2010
Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-β
H You, W Ding, CB Rountree
Hepatology 2010
Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications
JU Marquardt, VM Factor, SS Thorgeirsson
Journal of Hepatology 2010
Cell surface markers in colorectal cancer prognosis
L Belov, J Zhou, RI Christopherson
International journal of molecular sciences 2010
Enteric Bacteria and Cancer Stem Cells
J Sun
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Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties
EL Leung, RR Fiscus, JW Tung, VP Tin, LC Cheng, AD Sihoe, LM Fink, Y Ma, MP Wong
PloS one 2010
Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells
I Herrmann, PA Baeuerle, M Friedrich, A Murr, S Filusch, D Rüttinger, MW Majdoub, S Sharma, P Kufer, T Raum, M Münz
PloS one 2010
Mouse tissues express multiple splice variants of prominin-1
K Kemper, MJ Tol, JP Medema
PloS one 2010
Therapeutic implications of colon cancer stem cells
E Fabrizi, S Martino, F Pelacchi, L Ricci-Vitiani
World journal of gastroenterology : WJG 2010
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A Lugli, G Iezzi, I Hostettler, MG Muraro, V Mele, L Tornillo, V Carafa, G Spagnoli, L Terracciano, I Zlobec
British Journal of Cancer 2010
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N Navarro-Alvarez, E Kondo, H Kawamoto, W Hassan, T Yuasa, Y Kubota, M Seita, H Nakahara, T Hayashi, Y Nishikawa, RA Hassan, SM Javed, H Noguchi, S Matsumoto, S Nakaji, N Tanaka, N Kobayashi, A Soto-Gutierrez
Cell transplantation 2010
The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer
TM Elsaba, L Martinez-Pomares, AR Robins, S Crook, R Seth, D Jackson, A McCart, AR Silver, IP Tomlinson, M Ilyas
PloS one 2010
Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma
P Zhao, Y Li, Y Lu
BMC Cancer 2010
CD133 expression in chemo-resistant Ewing sarcoma cells
X Jiang, Y Gwye, D Russell, C Cao, D Douglas, L Hung, H Kovar, TJ Triche, ER Lawlor
BMC Cancer 2010
New promising drug targets in cancer- and metastasis-initiating cells
M Mimeault, SK Batra
Drug Discovery Today 2010
Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery
DD Fang, YJ Kim, CN Lee, S Aggarwal, K McKinnon, D Mesmer, J Norton, CE Birse, T He, SM Ruben, PA Moore
British Journal of Cancer 2010
Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy
JP Sullivan, JD Minna, JW Shay
Cancer metastasis reviews 2010
Glioma-associated cancer-initiating cells induce immunosuppression
J Wei, J Barr, LY Kong, Y Wang, A Wu, AK Sharma, J Gumin, V Henry, H Colman, R Sawaya, FF Lang, AB Heimberger
Clinical cancer research 2010
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J Wei, J Barr, LY Kong, Y Wang, A Wu, AK Sharma, J Gumin, V Henry, H Colman, W Priebe, R Sawaya, FF Lang, AB Heimberger
Molecular cancer therapeutics 2010
Concise Review: Kidney Stem/Progenitor Cells: Differentiate, Sort Out, or Reprogram?
O Pleniceanu, O Harari-Steinberg, B Dekel
Stem Cells 2010
Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on Notch signaling
JP Sullivan, M Spinola, M Dodge, MG Raso, C Behrens, B Gao, K Schuster, C Shao, JE Larsen, LA Sullivan, S Honorio, Y Xie, PP Scaglioni, JM DiMaio, AF Gazdar, JW Shay, II Wistuba, JD Minna
Cancer research 2010
Glioma cancer stem cells induce immunosuppressive macrophages/microglia
A Wu, J Wei, LY Kong, Y Wang, W Priebe, W Qiao, R Sawaya, AB Heimberger
Neuro-Oncology 2010
The Difficulty of Targeting Cancer Stem Cell Niches
MA LaBarge
Clinical cancer research 2010
New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in 3D cancer spheroids induced by purified colon tumor-initiating cells
GI Botchkina, ES Zuniga, M Das, Y Wang, H Wang, S Zhu, AG Savitt, RA Rowehl, Y Leyfman, J Ju, K Shroyer, I Ojima
Molecular Cancer 2010
Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells
B Song, Y Wang, MA Titmus, G Botchkina, A Formentini, M Kornmann, J Ju
Molecular Cancer 2010
Cancer stem cells in pancreatic cancer
Q Bao, Y Zhao, A Renner, H Niess, H Seeliger, KW Jauch, CJ Bruns
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In situ protein expression in tumour spheres: development of an immunostaining protocol for confocal microscopy
LB Weiswald, JM Guinebretière, S Richon, D Bellet, B Saubaméa, V Dangles-Marie
BMC Cancer 2010
Stem cells and cancer of the stomach and intestine
RG Vries, M Huch, H Clevers
Molecular Oncology 2010
Pancreatic cancer stem cells - update and future perspectives
E Lonardo, PC Hermann, C Heeschen
Molecular Oncology 2010
Cancer stem cells in solid tumors: elusive or illusive?
Y Welte, J Adjaye, HR Lehrach, CR Regenbrecht
Cell Communication and Signaling 2010
Tumor-initiating and -propagating cells: cells that we would like to identify and control.
Tysnes BB
Neoplasia (New York, N.Y.) 2010
Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies
Mimeault M, Batra SK
Anti-cancer agents in medicinal chemistry 2010
New advances on critical implications of tumor- and metastasis-initiating cells in cancer progression, treatment resistance and disease recurrence
Mimeault M, Batra SK
Histology and histopathology 2010
CD133(+) single cell-derived progenies of colorectal cancer cell line SW480 with different invasive and metastatic potential.
Li G, Liu C, Yuan J, Xiao X, Tang N, Hao J, Wang H, Bian X, Deng Y, Ding Y
Clinical & Experimental Metastasis 2010
Stem cells in colon cancer. A new era in cancer theory begins.
Papailiou J, Bramis KJ, Gazouli M, Theodoropoulos G
International Journal of Colorectal Disease 2010
Proliferation characteristics of CD133+ cell population in colorectal cancer.
Yu D, Zhang Y, Zou Y, Qin J, Li X, Xiao H, Tao D, Hu J, Gong J
2010
Molecular identification and targeting of colorectal cancer stem cells.
Kemper K, Grandela C, Medema JP
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The probable role of tumor stem cells for lymph node metastasis in supraglottic carcinoma.
Lu S, Tian J, Lv Z, Wang H, Bai X, Liu W, Li J, Xu W
Pathology oncology research : POR 2010
Molecular identification and targeting of colorectal cancer stem cells
Kemper K, Grandela C, Medema JP
Oncotarget 2010

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