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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 2015 (29)

Title and authors Publication Year
Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis
F Sipos
World journal of gastroenterology : WJG 2015
Induction of the intestinal stem cell signature gene SMOC-2 is required for L1-mediated colon cancer progression
A Shvab, G Haase, A Ben-Shmuel, N Gavert, T Brabletz, S Dedhar, A Ben-Ze'ev
Oncogene 2015
Advances in Experimental Medicine and Biology
S Singh, J Arcaroli, DC Thompson, W Messersmith, V Vasiliou
Advances in experimental medicine and biology 2015
Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance
P Zizza, C Cingolani, S Artuso, E Salvati, A Rizzo, C D'Angelo, M Porru, B Pagano, J Amato, A Randazzo, E Novellino, A Stoppacciaro, E Gilson, G Stassi, C Leonetti, A Biroccio
Nucleic Acids Research 2015
Characterization and Propagation of Tumor Initiating Cells Derived from Colorectal Liver Metastases: Trials, Tribulations and a Cautionary Note
MI James, LM Howells, A Karmokar, JA Higgins, P Greaves, H Cai, A Dennison, M Metcalfe, G Garcea, DM Lloyd, DP Berry, WP Steward, K Brown, YJ LEE
PloS one 2015
Spherical Cancer Models in Tumor Biology
LB Weiswald, D Bellet, V Dangles-Marie
Neoplasia (New York, N.Y.) 2015
Human non-small cell lung cancer expresses putative cancer stem cell markers and exhibits the transcriptomic profile of multipotent cells
N Zakaria, NM Yusoff, Z Zakaria, MN Lim, PJ Baharuddin, KS Fakiruddin, B Yahaya
BMC Cancer 2015
Impact of diabetes type II and chronic inflammation on pancreatic cancer
D Zechner, T Radecke, J Amme, F Bürtin, AC Albert, LI Partecke, B Vollmar
BMC Cancer 2015
Metastatic colon cancer cell populations contain more cancer stem‑like cells with a higher susceptibility to natural killer cell‑mediated lysis compared with primary colon cancer cells
G Kim, GH Ha, JH Bae, SO Oh, SH Kim, CD Kang
Oncology Letters 2015
Tenascin-C: A Novel Candidate Marker for Cancer Stem Cells in Glioblastoma Identified by Tissue Microarrays
S Nie, M Gurrea, J Zhu, S Thakolwiboon, JA Heth, KM Muraszko, X Fan, DM Lubman
Journal of Proteome Research 2015
Commentary: “Prom1 Function in Development, Intestinal Inflammation, and Intestinal Tumorigenesis”
CA Fargeas, E Büttner, D Corbeil
Frontiers in Oncology 2015
B7H1 Expression and Epithelial-To-Mesenchymal Transition Phenotypes on Colorectal Cancer Stem-Like Cells
Y Zhi, Z Mou, J Chen, Y He, H Dong, X Fu, Y Wu, G Pirozzi
PloS one 2015
Bidirectional interconversion of stem and non-stem cancer cell populations: A reassessment of theoretical models for tumor heterogeneity
SM van Neerven, M Tieken, L Vermeulen, MF Bijlsma
Molecular & Cellular Oncology 2015
Lgr5 expression is a valuable prognostic factor for colorectal cancer: evidence from a meta-analysis
Y Jiang, W Li, X He, H Zhang, F Jiang, Z Chen
BMC Cancer 2015
Expression of Oct‑4 is significantly associated with the development and prognosis of colorectal cancer
H Zhou, Y Hu, W Wang, Y Mao, J Zhu, B Zhou, J Sun, X Zhang
Oncology Letters 2015
Therapies targeting cancer stem cells: Current trends and future challenges
Denisa L Dragu, Laura G Necula, Coralia Bleotu, Carmen C Diaconu, Mihaela Chivu-Economescu
World journal of stem cells 2015
Fate of Prominin-1 Expressing Dermal Papilla Cells during Homeostasis, Wound Healing and Wnt Activation
GS Kaushal, E Rognoni, BM Lichtenberger, RR Driskell, K Kretzschmar, E Hoste, FM Watt
Journal of Investigative Dermatology 2015
Epigenetic and Immune Regulation of Colorectal Cancer Stem Cells
AV Paschall, K Liu
Current Colorectal Cancer Reports 2015
Molecular targets and pathways involved in liver metastasis of colorectal cancer
UH Weidle, F Birzele, A Krüger
Clinical & Experimental Metastasis 2015
Biomarkers and signaling pathways of colorectal cancer stem cells
D Abetov, Z Mustapova, T Saliev, D Bulanin
Tumor Biology 2015
Clusterin, a gene enriched in intestinal stem cells, is required for L1-mediated colon cancer metastasis
Shapiro B, Tocci P, Haase G, Gavert N, Ben-Ze'ev A
Oncotarget 2015
The metastasis suppressor, NDRG1, inhibits “stemness” of colorectal cancer via down-regulation of nuclear β-catenin and CD44
Wangpu X, Yang X, Zhao J, Lu J, Guan S, Lu J, Kovacevic Z, Liu W, Mi L, Jin R, Sun J, Yue F, Ma J, Lu A, Richardson DR, Wang L, Zheng M
Oncotarget 2015
CD133 overexpression correlates with clinicopathological features of gastric cancer patients and its impact on survival: A systematic review and meta-analysis
Yiming L, Yunshan G, Bo M, Yu Z, Tao W, Gengfang L, Dexian F, Shiqian C, Jianli J, Juan T, Zhinan C
Oncotarget 2015
Therapeutics targeting CD90-integrin-AMPK-CD133 signal axis in liver cancer
Chen WC, Chang YS, Hsu HP, Yen MC, Huang HL, Cho CY, Wang CY, Weng TY, Lai PT, Chen CS, Lin YJ, Lai MD
Oncotarget 2015
Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors.
Ayadi M, Bouygues A, Ouaret D, Ferrand N, Chouaib S, Thiery JP, Muchardt C, Sabbah M, Larsen AK
Oncotarget 2015
BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation.
Kim BR, Oh SC, Lee DH, Kim JL, Lee SY, Kang MH, Lee SI, Kang S, Joung SY, Min BW
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2015
Cancer stem cell targeted therapy: progress amid controversies
Wang T, Shigdar S, Gantier MP, Hou Y, Wang L, Li Y, Shamaileh HA, Yin W, Zhou SF, Zhao X, Duan W
Oncotarget 2015
Cancer stem cells in human digestive tract malignancies.
Rassouli FB, Matin MM, Saeinasab M
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2015
Clinical influence of cancer stem cells on residual disease after preoperative chemoradiotherapy for rectal cancer.
Yoon G, Kim SM, Kim HJ, Seo AN
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2015

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