Liver cancer stem cells as an important target in liver cancer therapies.
ABSTRACT Hepatic cancer is one of most common cause of cancer-related death. Hepato-epithelial cancers are believed to originate from the malignant transformation of liver-resident stem/progenitor cells. Liver cancer stem cells have been characterized recently and the phenotype of liver cancer stem cells has been defined as CD133+ CD44+ cancer cells. Recently, it has been also demonstrated about the relevance of targeting liver cancer stem cells, due to cancer stem cells are related to cancer metastasis. These advances no doubt to bring the new strategy in liver cancer treatment and control in this disease. This review describes the current status and progress about cancer stem cell research in liver and discuss of the implications of these studies in new liver cancer treatment strategies.
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Article: CD44 in hematological neoplasias.[Show abstract] [Hide abstract]
ABSTRACT: The CD44 protein family spans a large group of transmembrane glycoproteins acquired by alternative splicing and post-translational modifications. The great heterogeneity in molecular structure is reflected in its various important functions: CD44 mediates (1) interaction between cell and extracellular matrix, (2) signal submission, e.g., by acting as co-receptor for membrane-spanning receptor tyrosine kinases or by association with intracellular molecules initiating several signaling pathways, and (3) anchor function connecting to the cytoskeleton via the ezrin-radixin-moesin protein family. The expression pattern of the different CD44 isoforms display strong variations dependent on cell type, state of activation, and differentiation stage. In hematopoietic cells, CD44 mediates interaction of progenitor cells and bone marrow stroma during hematopoiesis, regulates maturation, and activation-induced cell death in T cells, influences neutrophil and macrophage migration as well as cytokine production, and participates in lymphocyte extravasation and migration. CD44 is involved in development and progress of hematological neoplasias by enhancement of apoptotic resistance, invasiveness, as well as regulation of bone marrow homing, and mobilization of leukemia-initiating cells into the peripheral blood. Thereby altered CD44 expression functions as marker for worse prognosis in most hematological malignancies. Additionally, CD44 expression levels can be used to distinguish between different hematological neoplasias and subtypes. Concerning new treatment strategies, CD44 displays promising potential either by direct targeting of CD44 expressed on the malignant cells or reversing an acquired resistance to primary treatment mediated through altered CD44 expression. The former can be achieved by antibody or hyaluronan-based immunotherapy.Annals of Hematology 05/2011; 90(5):493-508. · 2.40 Impact Factor
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ABSTRACT: Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β-catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM(+) cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM(+) cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β-catenin. Consequently, transcriptional activity of β-catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β-catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. © 2013 Wiley Periodicals, Inc.Molecular Carcinogenesis 07/2013; · 4.27 Impact Factor
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ABSTRACT: To isolate the CD133+CD44+ cells from human tongue squamous cell carcinoma (TSCC) Tca8113 cell line and investigate biological characteristics of them. Immunomagnetic microbeads were applied to sort the CD133+CD44+ cells. Flow cytometry was used to detect isolation purity. The proliferation, clone-formation efficiencies, invasion and migration, gene expressions, and tumor-formation abilities were analyzed among CD133+CD44+, CD133-CD44-, and total population of cells. The average purities of CD133+ and CD44+ cells reached 97.3% and 98.7%, respectively. The proliferation of CD133+CD44+ cells was significantly higher than the other two groups. The clone-forming efficiency of three groups was 70%, 8%, and 14%, respectively. The average invaded and migrated cell numbers of CD133+CD44+ and total population cells were 132 and 36.2, 311.6, and 156.2, respectively. The expressions of Bcl-2 and Sox2 in CD133+CD44+ cells were significantly higher than those in total population cells. A total of 10(4) CD133+CD44+ cells could form secondary tumors in nude mice, while the total population group needed 10(6) cells. The CD133+CD44+ subpopulation cells possess stem-like characteristics. They appear to be the potential targets for future biology therapy of human TSCC.Oral Diseases 03/2012; 18(2):169-77. · 2.40 Impact Factor