Identification of Putative Stem Cell Markers, CD133 and CXCR4, in hTERT–Immortalized Primary Nonmalignant and Malignant Tumor-Derived Human Prostate Epithelial Cell Lines and in Prostate Cancer Specimens

Miki, Jun; Furusato, Bungo; Li, Hongzhen; Gu, Yongpeng; Takahashi, Hiroyuki; Egawa, Shin; Sesterhenn, Isabell A.; McLeod, David G.; Srivastava, Shiv; Rhim, Johng S.

doi:10.1158/0008-5472.can-06-4429

Cited by 329 publications

(301 citation statements)

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“…The CXCR4 protein has multiple essential functions, including homing of stem cells and metastasis of cancer cells (Miki et al, 2007). Several cancers express CXCR4, and a relationship between CXCR4 expression and malignant potentiality has been suggested (Muller et al, 2001;Kaifi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…However, the possible clinical significance of CD133 expression in pancreatic cancer has not been investigated using immunohistochemistry, which is considered a difficult technique because of the inability to detect small numbers of putative stem cells (Miki et al, 2007). Nevertheless, immunostained cells may reflect the original features of cells in the tissue, so we used this approach in the present study to detect CD133-positive cells in paraffinembedded specimens from pancreatic cancer patients.…”

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confidence: 99%

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CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

et al. 2008

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Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P ¼ 0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P ¼ 0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P ¼ 0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P ¼ 0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

et al. 2008

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“…Subsequently, a wide range of stem cells, including meschenymal stem cells (Prockop, 1997), neural stem cells (Reynolds and Weiss, 1992), and amniotic fluid stem cells (De Coppi et al, 2007), were isolated from embryonic and adult tissues. Moreover, numerous reports have appeared within the past 10 years describing the isolation of stem cells from tumors of the breast (Al-Hajj et al, 2003), brain (Singh et al, 2003), prostate (Miki et al, 2007), and pancreas (Li C. et al, 2007), as well as several types of leukemia (Lapidot et al, 1994;Jamieson et al, 2004). Although work with acute myeloid leukemia in the 1990s (Lapidot et al, 1994) is often cited as the first definitive proof of tumor stem cells, EC cells were shown by single cell transplantation studies to be the stem cells of teratocarcinomas in the 1960s (Kleinsmith and Pierce, 1964).…”

Section: Stem Cells and Their Basic Propertiesmentioning

confidence: 99%

A challenge for regenerative medicine: Proper genetic programming, not cellular mimicry

Rizzino

2007

Developmental Dynamics

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Recent progress in stem cell biology and the reprogramming of somatic cells to a pluripotent phenotype has generated a new wave of excitement in regenerative medicine. Nonetheless, efforts aimed at understanding transdifferentiation, dedifferentiation, and the plasticity of cells, as well as the ability of somatic cells to be reprogrammed, has raised as many questions as those that have been answered. This review proffers the argument that many reports of transdifferentiation, dedifferentiation, and unexpected stem cell plasticity may be due to aberrant processes that lead to cellular look-alikes (cellular mimicry). In most cases, cellular look-alikes can now be identified readily by monitoring gene expression profiles, as well as epigenetic modifications of DNA and histone proteins of the cells involved. This review further argues that progress in regenerative medicine will be significantly hampered by failing to address the issue of cellular look-alikes.

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“…The pentaspan transmembrane glycoprotein CD133, also known as Prominin-1, was originally described as a hematopoietic stem cell marker (Yin et al, 1997) and was subsequently shown to be expressed by a number of progenitor cells including those of the epithelium, where it is expressed on the apical surface (Corbeil et al, 2000). CD133 expression distinguishes a number of cancer-initiating cells, including those associated with brain (Singh et al, 2004;Liu et al, 2006), pancreatic (Olempska et al, 2007), liver (Ma et al, 2002;Yin et al, 2007), skin (Monzani et al, 2007), prostate (Collins et al, 2005;Miki et al, 2007) and colon cancers (O'Brien et al, 2007;Ricci-Vitiani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells

et al. 2008

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The cancer stem cell hypothesis posits that malignant growth arises from a rare population of progenitor cells within a tumor that provide it with unlimited regenerative capacity. Such cells also possess increased resistance to chemotherapeutic agents. Resurgence of chemoresistant disease after primary therapy typifies epithelial ovarian cancer and may be attributable to residual cancer stem cells, or cancer-initiating cells, that survive initial treatment. As the cell surface marker CD133 identifies cancerinitiating cells in a number of other malignancies, we sought to determine the potential role of CD133 þ cells in epithelial ovarian cancer. We detected CD133 on ovarian cancer cell lines, in primary cancers and on purified epithelial cells from ascitic fluid of ovarian cancer patients. We found CD133 þ ovarian cancer cells generate both CD133 þ and CD133À daughter cells, whereas CD133À cells divide symmetrically. CD133 þ cells exhibit enhanced resistance to platinum-based therapy, drugs commonly used as first-line agents for the treatment of ovarian cancer. Sorted CD133 þ ovarian cancer cells also form more aggressive tumor xenografts at a lower inoculum than their CD133À progeny. Epigenetic changes may be integral to the behavior of cancer progenitor cells and their progeny. In this regard, we found that CD133 transcription is controlled by both histone modifications and promoter methylation. Sorted CD133À ovarian cancer cells treated with DNA methyltransferase and histone deacetylase inhibitors show a synergistic increase in cell surface CD133 expression. Moreover, DNA methylation at the ovarian tissue active P2 promoter is inversely correlated with CD133 transcription. We also found that promoter methylation increases in CD133À progeny of CD133 þ cells, with CD133 þ cells retaining a less methylated or unmethylated state. Taken together, our results show that CD133 expression in ovarian cancer is directly regulated by epigenetic modifications and support the idea that CD133demarcates an ovarian cancer-initiating cell population. The activity of these cells may be epigenetically detected and such cells might serve as pertinent chemotherapeutic targets for reducing disease recurrence.

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Identification of Putative Stem Cell Markers, CD133 and CXCR4, in hTERT–Immortalized Primary Nonmalignant and Malignant Tumor-Derived Human Prostate Epithelial Cell Lines and in Prostate Cancer Specimens

Cited by 329 publications

References 46 publications

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

A challenge for regenerative medicine: Proper genetic programming, not cellular mimicry

Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells

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