Liver Cancer Stem Cells

Sell, Stewart; Leffert, Hyam L.

doi:10.1200/jco.2007.15.5945

Cited by 216 publications

(166 citation statements)

References 72 publications

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“…First, an abundant oval cell response is likely to contribute to enhanced liver tumor formation in mice with attenuated hippo signaling activity. Oval cells are bipotental hepatic progenitor cells that are induced following carcinogen exposure in experimental models of hepatocellular carcinoma and are thought to function as cancer stem cells in these models (28,29). That we observe tumors of both biliary and hepatocyte lineages in sav1 mutant mice is consistent with an important contribution of oval cell activation in tumor formation.…”

Section: Transcripts Affected By Reduced Hippo Signaling In Hepatocytsupporting

confidence: 68%

Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver

Liu

Kim

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

656

636

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How organ size is controlled in mammals is not currently understood. In Drosophila the Hippo signaling pathway functions to suppress growth in imaginal discs and has been suggested to control organ size. To investigate the role of hippo signaling in regulation of mammalian organ size we have generated conditional alleles of Sav1 , mst1 , and mst2 , orthologs of Drosophila Salvador and hippo , respectively. Specific deletion of both mst1 and mst2 in hepatocytes results in significantly enlarged livers due to excessive proliferation. By the age of 5–6 months, mst1/2 conditional mutant livers have multiple foci of liver tumors, indicating that the combined activities of mst1 and mst2 act as redundant tumor suppressors in hepatocytes. Similar findings were obtained with liver-specific deletion of Sav1 , a second core Hippo signaling component that facilitates activation of mst1 and mst2 . Tumors from sav1 mutants exhibited varied morphology, suggesting a mixed-lineage origin of tumor-initiating cells. Transcriptional profiling of liver tissues from both mst1/2 and sav1 conditional mutants revealed a network of Hippo signaling regulated genes with specific enrichment for genes involved in immune and inflammatory responses. Histological and immunological characterization of mst1/2 double mutant liver tissues revealed abundant accumulation of adult facultative stem cells termed oval cells in periductal regions. Because oval cells induction is commonly associated with liver injury and tumor formation, it is likely that these cells contribute to the enlarged livers and hepatomas that we observe in sav1 and mst1/2 mutants. Taken together, our results demonstrate that the Hippo signaling pathway is a critical regulator of mammalian liver growth and a potent suppressor of liver tumor formation.

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Section: Transcripts Affected By Reduced Hippo Signaling In Hepatocytsupporting

confidence: 68%

Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver

Liu

Kim

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

656

636

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“…The liver is a good objective for studying tissue stem cell differentiation into tumor tissue cells in vitro [55], since several stem cells lines can differentiate and regenerate into functional liver cells [59] , and effective hepatic differentiation protocols have already been established [49][50][51][52][53]60]. It has also been demonstrated that the in vitro produced hepatocyte-like cells transplanted into patients can differentiate into functional liver cells [6].…”

Section: Discussionmentioning

confidence: 99%

“…Stem cell lines can be differentiated to hepatocyte-like cells implementing an in vitro model for the cancer cell formation from tissue stem cells [55]. During the differentiation process the continuous changes in the expression level of various genes can also be monitored [18,23,[56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Erdélyi-Belle

Török

Apáti

et al. 2015

Pathol. Oncol. Res.

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“…HepG2 was Cytotechnology (2015) 67:1-12 7 isolated from liver biopsy specimens of primary HB, whereas Hep3B was from primary HCC (Aden et al 1979;Knowles et al 1980). According to a hierarchical hepatic cellular lineage model for liver cell maturation and liver cancer development, HB is derived from neonatal liver stem cells with more potential and HCC is arisen from more differentiated mature hepatocytes in liver lobule (Sell and Leffert 2008). Hence, HepG2 and Hep3B come from different differentiation stages in liver cell lineage, which may well explain the differences between them.…”

Section: Underlying Mechanisms Responsible For the Differences Betweementioning

confidence: 99%

Distinctive pharmacological differences between liver cancer cell lines HepG2 and Hep3B

et al. 2014

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As cellular models for in vitro liver cancer and toxicity studies, HepG2 and Hep3B are the two most frequently used liver cancer cell lines. Because of their similarities they are often treated as the same in experimental studies. However, there are many differences that have been largely over-sighted or ignored between them. In this review, we summarize the differences between HepG2 and Hep3B cell lines that can be found in the literature based on PubMed search. We particularly focus on the differential gene expression, differential drug responses (chemosensitivity, cell cycle and growth inhibition, and gene induction), signaling pathways associated with these differences, as well as the factors in governing these differences between HepG2 and Hep3B cell lines. Based on our analyses of the available data, we suggest that neither HBx nor p53 may be the crucial factor to determine the differences between HepG2 and Hep3B cell lines although HBx regulates the expression of the majority of genes that are differentially expressed between HepG2 and Hep3B. Instead, the different maturation stages in cancer development of the original specimen between HepG2 and Hep3B may be responsible for the differences between them. This review provides insight into the molecular mechanisms underlying the differences between HepG2 and Hep3B and help investigators especially the beginners in the areas of liver cancer research and drug metabolism to fully understand, and thus better use and interpret the data from these two cell lines in their studies.

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Liver Cancer Stem Cells

Cited by 216 publications

References 72 publications

Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver

Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver

Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells

Distinctive pharmacological differences between liver cancer cell lines HepG2 and Hep3B

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