Multiple cellular origins and molecular evolution of intrahepatic cholangiocarcinoma

Wei, Miaoyan; Liu, Lisheng; Lin, Pei-Yi; Chen, Zhisheng; Quan, Zhiwei; Tang, Zhaohui

doi:10.1016/j.canlet.2016.02.038

Cited by 32 publications

(25 citation statements)

References 104 publications

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“…Recent research has brought up several new insights into the cellular origin of iCC (referring to a normal cell that acquires the first cancer-initiating mutation), indicative of possible multiple cell lineages origin (32,33). Histogenesis complexity and different molecular mechanisms underlying the diverse growth patterns of this malignancy is an object of clinical concern.…”

Section: Recent Data About Cells Of Origin If Iccsmentioning

confidence: 99%

“…iCC may develop from intrahepatic epithelial lining of small to large BD and PBGs (32,33), from malignant transformation of ductules, from HPCs of canal of Hering or periductal glands stem niche or through oncogenic reprogramming of adult hepatocytes. However, these conclusions are largely based on reliance on results from murine models of lineage tracing systems which have some known technical limitations.…”

Section: Recent Data About Cells Of Origin If Iccsmentioning

confidence: 99%

See 1 more Smart Citation

Pathology of intrahepatic cholangiocarcinoma

Vijgen¹,

Terris²,

Rubbia‐Brandt³

2017

Hepatobiliary Surg. Nutr.

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Section: Recent Data About Cells Of Origin If Iccsmentioning

confidence: 99%

Section: Recent Data About Cells Of Origin If Iccsmentioning

confidence: 99%

Pathology of intrahepatic cholangiocarcinoma

Vijgen¹,

Terris²,

Rubbia‐Brandt³

2017

Hepatobiliary Surg. Nutr.

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“…Indeed, primary biliary cholangitis massively activates hepatic progenitor cells and only minimally activates PBGs, while the opposite has been described in primary sclerosing cholangitis. 166 Since somatic mutagenesis and epigenome features are cell/lineage specific 95,167 and are driven by the inflammatory pathological milieu characterizing the CCA risk factors, 74 the multiple niches of origin plus the specific related genomic alterations may explain the intertumoural heterogeneity observed at any level of CCA, including molecular clustering ( Figure 2).…”

Section: Interaction Between Cells Of Origin Molecular Alterationsmentioning

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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“…Mature hepatocytes have the ability to de-differentiate into more pluripotent cells through mechanisms of cell plasticity and reprogramming, thereby acting as a population with stem cell traits[23]. IHC is categorized as a primary liver tumor and shows characteristics of both hepatocellular carcinoma and cholangiocarcinoma, suggesting a potential link regarding the cell of origin[24,25]. Evidence for mature hepatocytes being the source and quasi-CSC for IHC comes from two studies that showed that mature hepatocytes are able to transdifferentiate and form IHC[9,10].…”

Section: Potential Origins Of Biliary Tract Cancer Cells With Stem Cementioning

confidence: 99%

“…It was shown that under chronic inflammatory conditions, neoplastic cholangiocytes are able to produce and secrete IL-6 in an autocrine loop, resulting in proliferation and induction of DNA damaging molecules such as reactive oxygen species and nitric oxide[24]. The JAK/STAT signaling cascade is one of the downstream pathways that is activated via inflammation-related cytokines in BTC development[93,94].…”

Section: Relevance Of Stemness Pathways In Biliary Tract Cancer Stem mentioning

confidence: 99%

Biliary tract cancer stem cells - translational options and challenges

Mayr

Ocker

Ritter

et al. 2017

WJG

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Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells - the cancer stem cells - possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.

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Multiple cellular origins and molecular evolution of intrahepatic cholangiocarcinoma

Cited by 32 publications

References 104 publications

Pathology of intrahepatic cholangiocarcinoma

Pathology of intrahepatic cholangiocarcinoma

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

Biliary tract cancer stem cells - translational options and challenges

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