MAPK/ERK and Wnt/β-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

Jin, Can; Samuelson, Lisa; Cui, Cai Bin; Sun, Yang-Zhong; Gerber, David A.

doi:10.1016/j.bbrc.2011.05.094

Cited by 30 publications

(26 citation statements)

References 32 publications

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“…The concentration used was however sufficient to modulate the Erk1/2-dependant cellular impedance profile and in parallel induce the Erk1/2-dependant overexpression of CCND1. The link between Erk1/2 pathway and the regulation of CCND1 gene expression has already been shown (Jin et al, 2011). We can confirm that TCDD and Error bars indicate the mean ± SEM of triplicate determinations in three independent experiments.…”

Section: Discussionsupporting

confidence: 83%

Potential involvement of chemicals in liver cancer progression: An alternative toxicological approach combining biomarkers and innovative technologies

Peyre

Zucchini-Pascal

Sousa

et al. 2014

Toxicology in Vitro

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Section: Discussionsupporting

confidence: 83%

Potential involvement of chemicals in liver cancer progression: An alternative toxicological approach combining biomarkers and innovative technologies

Peyre

Zucchini-Pascal

Sousa

et al. 2014

Toxicology in Vitro

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“…The effect of macrophage deletion on the other pathways (e.g. JNK, ERK and WNT pathway) [43], [44] which is important to oval cell proliferation needs further studies. Oval cell mediated liver regeneration is a systematic program, and other liver nonparenchymal cells also contribute to OC expansion.…”

Section: Discussionmentioning

confidence: 99%

Oval Cell Response Is Attenuated by Depletion of Liver Resident Macrophages in the 2-AAF/Partial Hepatectomy Rat

et al. 2012

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Background/AimsMacrophages are known to play an important role in hepatocyte mediated liver regeneration by secreting inflammatory mediators. However, there is little information available on the role of resident macrophages in oval cell mediated liver regeneration. In the present study we aimed to investigate the role of macrophages in oval cell expansion induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) in rats.Methodology/Principal FindingsWe depleted macrophages in the liver of 2-AAF/PH treated rats by injecting liposome encapsulated clodronate 48 hours before PH. Regeneration of remnant liver mass, as well as proliferation and differentiation of oval cells were measured. We found that macrophage-depleted rats suffered higher mortality and liver transaminase levels. We also showed that depletion of macrophages yielded a significant decrease of EPCAM and PCK positive oval cells in immunohistochemical stained liver sections 9 days after PH. Meanwhile, oval cell differentiation was also attenuated as a result of macrophage depletion, as large foci of small basophilic hepatocytes were observed by day 9 following hepatectomy in control rats whereas they were almost absent in macrophage depleted rats. Accordingly, real-time polymerase chain reaction analysis showed lower expression of albumin mRNA in macrophage depleted livers. Then we assessed whether macrophage depletion may affect hepatic production of stimulating cytokines for liver regeneration. We showed that macrophage-depletion significantly inhibited hepatic expression of tumor necrosis factor-α and interleukin-6, along with a lack of signal transducer and activator of transcription 3 phosphorylation during the early period following hepatectomy.ConclusionsThese data indicate that macrophages play an important role in oval cell mediated liver regeneration in the 2-AAF/PH model.

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“…Sca-1-enriched prostate cells have multiple stem/ progenitor cell properties [40]. Sca-1-positive hepatic progenitor cells show a significant increase in proliferation and colony formation under epidermal growth factor stimulation [41].…”

Section: Other Potential Markersmentioning

confidence: 99%

“…The MAPK/ERK pathway is essential and critical for hepatic progenitor cell proliferation [41]. A report showed that disruption of the RAF/ MEK/MAPK pathway by a RAS or BRAF mutation was detected in more than 60 % of cholangiocarcinomas, indicating that these pathways are important in cholangiocarcinoma carcinogenesis [57].…”

Section: Raf/mek/mapk Signaling Pathwaymentioning

confidence: 99%

Recent advances in cancer stem cell research for cholangiocarcinoma

Kokuryo

Yokoyama

Nagino

2012

J Hepato Biliary Pancreat

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Cancer stem cells have been identified as cells with the capacity to self‐renew and differentiate into multiple lineages of human malignancies. Cholangiocarcinoma is one of the most difficult intra‐abdominal malignancies that can be treated using a surgical approach. Chemotherapy in addition to surgery is necessary to improve patient survival. However, its clinical benefit is limited, and, to date, no other effective anticancer drug is available for this disease. Several reports have shown the existence of cholangiocarcinoma stem cells. Cell surface antigens such as CD133, CD24, EpCAM, CD44, and others have been used to isolate cholangiocarcinoma stem cells. In general, enhanced expression of these markers in resected specimens of cholangiocarcinoma was associated with malignant potential. Distinct and specific pathways are expected to be present in cancer stem cells compared to other cancer cells that have no stem cell properties. To date, reports showing possible signaling pathways in cholangiocarcinoma stem cells are limited. More research is anticipated. Targeting therapies for surface molecular markers or specific signaling pathways of cholangiocarcinoma stem cells may be important in order to change the clinical outcome of patients with this disease. However, no clinical trial has been performed so far. This review will focus on the markers and signaling pathways used to define cholangiocarcinoma stem cells. A novel therapeutic approach of targeting cholangiocarcinoma stem cells will also be discussed.

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MAPK/ERK and Wnt/β-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

Cited by 30 publications

References 32 publications

Potential involvement of chemicals in liver cancer progression: An alternative toxicological approach combining biomarkers and innovative technologies

Potential involvement of chemicals in liver cancer progression: An alternative toxicological approach combining biomarkers and innovative technologies

Oval Cell Response Is Attenuated by Depletion of Liver Resident Macrophages in the 2-AAF/Partial Hepatectomy Rat

Recent advances in cancer stem cell research for cholangiocarcinoma

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