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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of prostate cancer stem cells offers a theoretical explanation for many of the enduring uncertainties surrounding the etiology and treatment of the most commonly diagnosed tumor in US males. The study of cancer stem cells in prostate, as in other complex tissues, is critically dependent on the availability of pure cell populations, a situation complicated by the heterogeneity of prostate tumors. However, selection of cells with a CD133(+)/alpha 2 beta 1 integrin/ CD44(+) phenotype enriches for a tumor-initiating population from human prostate cancers. Among the most pressing needs is for enduring therapy in patients who have experienced failure of hormonal treatments. Because the putative cancer stem cell does not express androgen receptor, it is likely to be immune from most androgen-based therapies, and an inherent genetic instability would enable the tumor to develop the new variants present in hormone-refractory disease. Prostate cancer stem cells have a unique gene expression signature that can also be related to Gleason grade and patient outcome. The scarcity of cancer stem cells in a prostate tumor will probably limit their usefulness in cancer diagnosis and prognosis. However, the emergence of new stem-cell therapeutic targets not only will require new assays for efficacy (because of their relatively quiescent nature), but also holds real promise of more lasting treatments to augment those currently directed against the remaining tumor cells, which comprise 99.9% of tumor mass, but paradoxically have a poor tumor-initiating capacity.
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PMID:Prostate cancer stem cells: a new target for therapy. 1895 54

Cells with stem-cell markers and features have recently been identified in melanoma tissues and cell lines. Melanoma stem-like cells possess many traits of tumor-initiating or tumor stem cells including self-renewal capacity, high tumorigenicity, and differentiation into various mesenchymal lineages, including melanocytic cells. Four subpopulations of melanoma-initiating cells have been distinguished: CD20(+), CD133(+), label-retaining or slow-cycling cells, and side-population cells with high efflux activities. Whether these are distinct or overlapping populations is currently under investigation. Ongoing studies are dissecting and characterizing the hierarchy of these subpopulations within a malignant lesion. Understanding these and the dynamics of clonal dominance will aid in the development of novel therapeutic strategies.
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PMID:Melanoma stem cells: the dark seed of melanoma. 1853 69

This study investigated the factors responsible for migration and homing of magnetically labeled AC133(+) cells at the sites of active angiogenesis in tumor. AC133(+) cells labeled with ferumoxide-protamine sulfate were mixed with either rat glioma or human melanoma cells and implanted in flank of nude mice. An MRI of the tumors including surrounding tissues was performed. Tumor sections were stained for Prussian blue (PB), platelet-derived growth factor (PDGF), hypoxia-inducible factor-1alpha (HIF-1alpha), stromal cell derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), and endothelial markers. Fresh snap-frozen strips from the central and peripheral parts of the tumor were collected for Western blotting. MRIs demonstrated hypointense regions at the periphery of the tumors where the PB(+)/AC133(+) cells were positive for endothelial cells markers. At the sites of PB(+)/AC133(+) cells, both HIF-1alpha and SDF-1 were strongly positive and PDGF and MMP-2 showed generalized expression in the tumor and surrounding tissues. There was no significant association of PB(+)/AC133(+) cell localization and VEGF expression in tumor cells. Western blot demonstrated strong expression of the SDF-1, MMP-2, and PDGF at the peripheral parts of the tumors. HIF-1alpha was expressed at both the periphery and central parts of the tumor. This work demonstrates that magnetically labeled cells can be used as probes for MRI and histological identification of administered cells.
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PMID:Detection of migration of locally implanted AC133+ stem cells by cellular magnetic resonance imaging with histological findings. 1855 61

A number of recent reports have demonstrated that only CD133-positive cancer cells of glioblastoma multiforme (GBM) have tumor-initiating potential. These findings raise an attractive hypothesis that GBMs can be cured by eradicating CD133-positive cancer stem cells (CSCs), which are a small portion of GBM cells. However, as GBMs are known to possess various genetic alterations, GBMs might harbor heterogeneous CSCs with different genetic alterations. Here, we compared the clinical characteristics of two GBM patient groups divided according to CD133-positive cell ratios. The CD133-low GBMs showed more invasive growth and gene expression profiles characteristic of mesenchymal or proliferative subtypes, whereas the CD133-high GBMs showed features of cortical and well-demarcated tumors and gene expressions typical of proneuronal subtype. Both CD133-positive and CD133-negative cells purified from four out of six GBM patients produced typical GBM tumor masses in NOD-SCID brains, whereas brain mass from CD133-negative cells showed more proliferative and angiogenic features compared to that from CD133-positive cells. Our results suggest, in contrast to previous reports that only CD133-positive cells of GBMs can initiate tumor formation in vivo CD133-negative cells also possess tumor-initiating potential, which is indicative of complexity in the identification of cancer cells for therapeutic targeting.
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PMID:Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas. 1856 Mar 66

The neural precursor surface marker CD133 is thought to be enriched in brain cancer stem cells and in radioresistant DAOY medulloblastoma-derived tumor cells. Given that membrane type-1 matrix metalloproteinase (MT1-MMP) expression is a hallmark of highly invasive, radioresistant, and hypoxic brain tumor cells, we sought to determine whether MT1-MMP and other MMPs could regulate the invasive phenotype of CD133(+) DAOY cells. We found that when DAOY medulloblastoma or U87 glioblastoma cells were implanted in nude mice, only those cells specifically implanted in the brain environment generated CD133(+) brain tumors. Vascular endothelial growth factor and basic fibroblast growth factor gene expression increases in correlation with CD133 expression in those tumors. When DAOY cultures were induced to generate in vitro neurosphere-like cells, gene expression of CD133, MT1-MMP, MMP-9, and MDR-1 was induced and correlated with an increase in neurosphere invasiveness. Specific small interfering RNA gene silencing of either MT1-MMP or MMP-9 reduced the capacity of the DAOY monolayers to generate neurospheres and concomitantly abrogated their invasive capacity. On the other hand, overexpression of MT1-MMP in DAOY triggered neurosphere-like formation which was further amplified when cells were cultured in neurosphere medium. Collectively, we show that both MT1-MMP and MMP-9 contribute to the invasive phenotype during CD133(+) neurosphere-like formation in medulloblastoma cells. Increases in MMP-9 may contribute to the opening of the blood-brain barrier, whereas increased MT1-MMP would promote brain tumor infiltration. Our study suggests that MMP-9 or MT1-MMP targeting may reduce the formation of brain tumor stem cells.
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PMID:Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. 1856 95

The cancer stem cell (CSC) hypothesis has provided insights into the initiation and recurrence of brain tumor. Specific identification and targeted elimination of these CSCs within the tumor mass represents a promising therapeutic strategy for refractory brain tumors. In this study, we attempted to identify CSCs in the rat C6 glioma cell line by three different identification methods. It is interesting to note that single-cell clonal analysis showed most C6 cells are cancer stem-like cells with characteristics of self-renewal, multilineage differentiation potentials in vitro, and tumorigenic capacity in vivo. It is surprising to note that CD133 failed to identify the total cancer stem-like cell population in the C6 line, since both CD133 (+) and CD133 (-) C6 cells have cancer stem-like cell fractions. Moreover, Hoechst 33342 staining, which is used in flow cytometry to isolate the side population (SP), was found to be harmful to C6 cells. Therefore, CD133 (-) and non-SP C6 cells may also harbor cancer stem-like cells. These results imply the limitation of using current identification methods in C6 line and underscore the importance of defining the genetic and molecular basis of CSCs.
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PMID:Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. 1859 36

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133(+)) and CD133-negative cells (LC-CD133(-)) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133(+) displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133(+), unlike LC-CD133(-), highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133(+) to form spheres and can further facilitate LC-CD133(+) to differentiate into LC-CD133(-). In addition, knock-down of Oct-4 expression in LC-CD133(+) can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133(+) can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133(+). Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133(+) and malignant lung cancer.
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PMID:Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. 1861 34

The aim of the present study was to investigate the localization and distribution of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV astrocytomas was undertaken. The immunohistochemical expression of CD133 in paraffin sections was analysed using morphometry. In all grades, CD133 was expressed on tumour and endothelial cells. Tumour cells were found in perivascular niches, as dispersed single cells and in pseudopalisade formations around necrosis. There was no correlation between the mean volume fraction of CD133(+) niches and all CD133(+) tumour cells and tumour grade. However, the volume fraction of CD133(+) blood vessels increased significantly from 0.4% in diffuse astrocytomas to 2.2% in glioblastomas. Neither of them was related to patient survival. Double immunofluorescence stainings showed that the CD133(+) niches both contained CD133(+) cells with and without co-expression of the intermediate filament protein marker nestin, and only few CD133(+)/MIB-1(+) proliferating cells were found. In conclusion, a CD133(+) perivascular stem cell-like entity exists in astrocytomas. CD133(+) tumour vessels may play an important role in a brain tumour stem cell context, while CD133 alone does not appear to be a specific tumour stem cell marker related to patient survival.
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PMID:CD133 identifies perivascular niches in grade II-IV astrocytomas. 1861

The prognosis of patients suffering from glioblastoma (GBM) is dismal despite multimodal therapy. Although chemotherapy with temozolomide may contain tumor growth for some months, invariable tumor recurrence suggests that cancer stem cells (CSC) maintaining these tumors persist. We have therefore investigated the effect of temozolomide on CD133(+) and CD133(-) GBM CSC lines. Although differentiated tumor cells constituting the bulk of all tumor cells were resistant to the cytotoxic effects of the substance, temozolomide induced a dose- and time-dependent decline of the stem cell subpopulation. Incubation with sublethal concentrations of temozolomide for 2 days completely depleted clonogenic tumor cells in vitro and substantially reduced tumorigenicity in vivo. In O(6)-methylguanine-DNA-methyltransferase (MGMT)-expressing CSC lines, this effect occurred at 10-fold higher doses compared with MGMT-negative CSC lines. Thus, temozolomide concentrations that are reached in patients were only sufficient to completely eliminate CSC in vitro from MGMT-negative but not from MGMT-positive tumors. Accordingly, our data strongly suggest that optimized temozolomide-based chemotherapeutic protocols might substantially improve the elimination of GBM stem cells and consequently prolong the survival of patients.
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PMID:Temozolomide preferentially depletes cancer stem cells in glioblastoma. 1962 70

Recent studies have found that cellular self-renewal capacity in brain cancer is heterogeneous, with only stem-like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem-like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem-like cells expressing Nestin, Musashi-1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet-derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. Our data point to adult brain precursor cells to be transformed in malignancies. Furthermore, in vitro expansion of adult neural stem cells, which will be mandatory for therapeutic strategies in neurological disorders, also harbors the risk for amplifying precursor cells with acquired genetic abnormalities and induction of malignant tumors after transplantation.
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PMID:Spontaneous in vitro transformation of adult neural precursors into stem-like cancer cells. 1863 11


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