Notch2 signaling and undifferentiated liver cancers: Evidence of hepatic stem/progenitor cell origin

Cardinale, Vincenzo; Carpino, Guido; Reíd, Lola M.; Gaudio, Eugenio; Alvaro, Domenico

doi:10.1002/hep.26280

Cited by 10 publications

(9 citation statements)

References 8 publications

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“…Another report demonstrated that HCC, in which NOTCH2 receptor participates, derives from immature biliary epithelial cells that transdifferentiate to hepatocytes (Spee et al., ). The expansion of these cells mimics the oncogenic activation of hepatic stem cells (Cardinale et al., ).…”

Section: The Role Of Notch Receptors and Their Ligands In The Developmentioning

confidence: 99%

The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma

Gil-García

Baladrón

2015

Biology of the Cell

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The NOTCH signalling pathway is one of the key molecular pathways of embryonic development and adult tissues homeostasis in mammals. Mammals have four NOTCH receptors and various ligands that modulate their activity. Many cell disorders, whose genesis involves the NOTCH signalling pathway, have been discovered, including cancer. The mechanisms by which these receptors and their ligands affect liver cell transformation are not yet well understood, and they seem to behave as both oncogenes and tumour-suppressor proteins. In this review, we discuss the published data regarding the role of these proteins in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma malignancies. The alteration of the NOTCH signalling pathway may be one of the main drivers of hepatic neoplastic growth. However, this signalling pathway might also modulate the development of specific liver tumour features. The complexity of the function of NOTCH receptors and their ligands may be due to their interactions with many other cell signalling pathways. Furthermore, the different levels of expression and activation of these receptors could be a reason for their distinct and sometimes contradictory effects.

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Section: The Role Of Notch Receptors and Their Ligands In The Developmentioning

confidence: 99%

The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma

Gil-García

Baladrón

2015

Biology of the Cell

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“…153 For example, a pathophysiological issue may arise with respect to the origin of primary liver cancers when the gene used for cell tracing can be expressed in multiple cells and lacks specificity. 161 Also, the experimental damage can induce specific hepatocyte alterations and mutagenesis, such as in the thioacetamide-induced mouse model (hepatotoxin was used in the study of HCC. 162 Technical issues, such as artifacts induced by tamoxifene administration should also be taken into account.…”

Section: Mouse Models For Tracing the Cellular Origin Of Ccamentioning

confidence: 99%

Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma

Vicent

Lieshout

Verstegen

et al. 2019

Liver International

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Human cholangiocarcinoma (CCA) is an aggressive tumour entity arising from the biliary tree, whose molecular pathogenesis remains largely undeciphered. Over the last decade, the advent of high‐throughput and cell‐based techniques has significantly increased our knowledge on the molecular mechanisms underlying this disease while, at the same time, unravelling CCA complexity. In particular, it becomes clear that CCA displays pronounced inter‐ and intratumoural heterogeneity, which is presumably the consequence of the interplay between distinct tissues and cells of origin, the underlying diseases, and the associated molecular alterations. To better characterize these events and to design novel and more effective therapeutic strategies, a number of CCA experimental and preclinical models have been developed and are currently generated. This review summarizes the current knowledge and understanding of these models, critically underlining their translational usefulness and limitations. Furthermore, this review aims to provide a comprehensive overview on cells of origin, cancers stem cells and their dynamic interplay within CCA tissue.

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“…2e, *P < 0.1 × 10 −4 ). Also pathways involved in stem cell development, including Wnt, Notch, and Hedgehog [19][20][21] were also enriched in MHPCs when compared to adult liver tissues (Supplementary Figure S2). These data indicate that MHPCs are genuine hepatic progenitor cells.…”

Section: Mhpcs Possess Hepatic Progenitor Cell-specific Expression Pamentioning

confidence: 99%

Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo

et al. 2018

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Common marmoset (Callithrix jacchus) is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening.

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Notch2 signaling and undifferentiated liver cancers: Evidence of hepatic stem/progenitor cell origin

Cited by 10 publications

References 8 publications

The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma

The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma

Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma

Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo

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