skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

Abstract

Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133{sup +} cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well.

Authors:
 [1];  [2]; ;  [1];  [1];  [2];  [3];  [1];  [1];  [2];  [1];  [4];  [5]
  1. Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld (Australia)
  2. (Czech Republic)
  3. Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague (Czech Republic)
  4. Laboratory of Apoptosis and Cell Signalling, Institute of Molecular Genetics, Czech Academy of Sciences, Prague (Czech Republic)
  5. Genomics Research Centre, School of Medical Science, Griffith University, Southport, Qld (Australia)
Publication Date:
OSTI Identifier:
20979878
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.01.159; PII: S0006-291X(07)00232-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; CHEMOTHERAPY; DRUGS; LYSOSOMES; MITOCHONDRIA; MOLECULAR BIOLOGY; NEOPLASMS; STEM CELLS

Citation Formats

Neuzil, Jiri, Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, E-mail: j.neuzil@griffith.edu.au, Stantic, Marina, Zobalova, Renata, Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Chladova, Jaromira, Wang, Xiufang, Prochazka, Lubomir, Veterinary Research Institute, Brno, Dong, Lanfeng, Andera, Ladislav, and Ralph, Stephen J. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.01.159.
Neuzil, Jiri, Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, E-mail: j.neuzil@griffith.edu.au, Stantic, Marina, Zobalova, Renata, Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Chladova, Jaromira, Wang, Xiufang, Prochazka, Lubomir, Veterinary Research Institute, Brno, Dong, Lanfeng, Andera, Ladislav, & Ralph, Stephen J. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?. United States. doi:10.1016/j.bbrc.2007.01.159.
Neuzil, Jiri, Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, E-mail: j.neuzil@griffith.edu.au, Stantic, Marina, Zobalova, Renata, Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Chladova, Jaromira, Wang, Xiufang, Prochazka, Lubomir, Veterinary Research Institute, Brno, Dong, Lanfeng, Andera, Ladislav, and Ralph, Stephen J. 2007. "Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?". United States. doi:10.1016/j.bbrc.2007.01.159.
@article{osti_20979878,
title = {Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?},
author = {Neuzil, Jiri and Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague and E-mail: j.neuzil@griffith.edu.au and Stantic, Marina and Zobalova, Renata and Molecular Therapy Group, Institute of Molecular Genetics, Czech Academy of Sciences, Prague and Chladova, Jaromira and Wang, Xiufang and Prochazka, Lubomir and Veterinary Research Institute, Brno and Dong, Lanfeng and Andera, Ladislav and Ralph, Stephen J.},
abstractNote = {Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133{sup +} cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well.},
doi = {10.1016/j.bbrc.2007.01.159},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 355,
place = {United States},
year = 2007,
month = 4
}
  • The CD133 antigen, identified as a hematopoietic stem cell marker, appears in various human embryonic epithelia including the neural tube, gut, and kidney. We herein investigated whether CD133{sup +} cells isolated from human hepatocellular carcinoma cell lines possess cancer stem/progenitor cell-like properties. Among the three cell lines studied, the CD133 antigen was found to be expressed only on the surface of Huh-7 cells. CD133{sup +} cells from Huh-7 performed a higher in vitro proliferative potential and lower mRNA expressions of mature hepatocyte markers, glutamine synthetase and cytochrome P450 3A4, than CD133{sup -} population of Huh-7 cells. When either CD133{sup +}more » or CD133{sup -} cells were subcutaneously injected into SCID mice, CD133{sup +} cells formed tumors, whereas CD133{sup -} cells induced either a very small number of tumors or none at all. Taken together, the identification of CD133{sup +} cells could thus be a potentially powerful tool to investigate the tumorigenic process in the hepatoma system and to also develop effective therapies targeted against hepatocellular carcinoma.« less
  • Highlights: Black-Right-Pointing-Pointer The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. Black-Right-Pointing-Pointer STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. Black-Right-Pointing-Pointer Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. Black-Right-Pointing-Pointer STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. Black-Right-Pointing-Pointer Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existencemore » of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH{sup +}/CD133{sup +}). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem-like cells and inhibition of STAT3 in cancer stem-like cells may offer a potential treatment for colorectal cancer.« less
  • Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, accounting for 80%–90% of all liver cancers. The disease ranks as the fifth most common cancer worldwide and is the third leading cause of all cancer-associated deaths. Although advances in HCC detection and treatment have increased the likelihood of a cure at early stages of the disease, HCC remains largely incurable because of late presentation and tumor recurrence. Only 25% of HCC patients are deemed suitable for curative treatment, with the overall survival at just a few months for inoperable patients. Apart from surgical resection, loco-regional ablationmore » and liver transplantation, current treatment protocols include conventional cytotoxic chemotherapy. But due to the highly resistant nature of the disease, the efficacy of the latter regimen is limited. The recent emergence of the cancer stem cell (CSC) concept lends insight into the explanation of why treatment with chemotherapy often may seem to be initially successful but results in not only a failure to eradicate the tumor but also possibly tumor relapse. Commonly used anti-cancer drugs in HCC work by targeting the rapidly proliferating and differentiated liver cancer cells that constitute the bulk of the tumor. However, a subset of CSCs exists within the tumor, which are more resistant and are able to survive and maintain residence after treatment, thus, growing and self-renewing to generate the development and spread of recurrent tumors in HCC. In the past few years, compelling evidence has emerged in support of the hierarchic CSC model for solid tumors, including HCC. And in particular, CD133 has drawn significant attention as a critical liver CSC marker. Understanding the characteristics and function of CD133{sup +} liver CSCs has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress in CD133{sup +} liver CSC research with regard to identification, regulation and clinical implications will be discussed.« less
  • Highlights: • Germ cell marker DDX4 was significantly increased in ovarian cancer. • Ovarian cancer stem cell marker CD133 was significantly increased in ovarian cancer. • DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. • CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4. • Germ cell marker DDX4 has the potential of ovarian cancer stem cell marker. - Abstract: DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondarymore » structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.« less
  • Purpose: Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line. Methods and Materials: Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed formore » marker stability, cell cycle distribution, and radiosensitivity. Results: CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the {beta}-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their {alpha}-parameters and cell cycle distributions were identical. Conclusions: Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response.« less