Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma

Vilchez, Valery; Turcios, Lilia; Zaytseva, Yekaterina Y.; Stewart, Rachel L.; Lee, Eun Y.; Maynard, Erin; Shah, Malay B.; Daily, Michael F.; Tzeng, Ching Wei D.; Davenport, Daniel L.; Castellanos, Ana Lia; Krohmer, Steven; Hosein, Peter J.; Evers, B. Mark; Gedaly, Roberto

doi:10.1016/j.amjsurg.2015.12.019

Cited by 18 publications

(9 citation statements)

References 28 publications

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“…When Wnt/β-catenin signaling is activated, β-catenin accumulates in the cytoplasm and then translocates into the nucleus, where it regulates the expression of downstream target genes to regulate the growth and survival of cells (22). Therefore, many antitumor drugs target Wnt/β-catenin signaling (27,42,43). A previous study has proved that accumulation of β-catenin in nuclear and/or cytoplasm occurred in OS cells, and the accumulation may be associated with the pathogenesis of OS (44).…”

Section: Discussionmentioning

confidence: 99%

Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells

Zhang

Tian

et al. 2016

International Journal of Oncology

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Although multiple chemotherapeutic agents have been used for osteosarcoma (OS) treatment, their mechanisms need further study. Ursolic acid (UA), a pentacyclic triterpenoid, can reduce cell proliferation and induce apoptosis in various cancer cells, such as OS. However, the exact mechanism underlying this function remains unclear. In this study, we investigated the anti‑proliferative effect of UA in human OS 143B cells and dissected the possible molecular mechanism underlying this effect. We demonstrated that UA can reduce cell proliferation, induce apoptosis and arrest cell cycle in 143B cells, as well as inhibit OS tumor growth in a mouse xenograft model. Using a luciferase reporter assay, we found that the Wnt/β‑catenin signaling is inhibited by UA in 143B cells. Correspondingly, the expression level and nuclear translocation of β‑catenin are both decreased by UA. Exogenous expression of β‑catenin attenuates the anticancer effect of UA in 143B cells, while knockdown of β‑catenin enhances this effect. UA increases the expression level of p53 in a concentration‑dependent manner, and inhibition of p53 reduces the anticancer effect of UA in 143B cells. Moreover, inhibition of p53 partly reverses the UA‑induced downregulation of β‑catenin, as do the targets of Wnt/β‑catenin signaling, such as c‑Myc and cyclin D1. Our findings indicated that UA can inhibit the proliferation of 143B OS cells through inactivation of Wnt/β-catenin signaling, which may be mediated partly by upregulating the expression of p53.

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Section: Discussionmentioning

confidence: 99%

Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells

Zhang

Tian

et al. 2016

International Journal of Oncology

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“…In human patients, CD44 + and CD133 + correlated with increased risk of poorly differentiated HCC and elevated alpha-fetoprotein levels. CD44 and CD133, alone or in combination with microvascular invasion, are independent predictors of poor prognosis in patients undergoing transplantation for HCC (77).…”

Section: Markers To Identify Lcscsmentioning

confidence: 99%

Cellular Origin of Hepatocellular Carcinoma

Schneller

Angel

2019

Hepatocellular Carcinoma

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Molecular features of hepatocellular carcinoma affect patient prognosis and treatment efficiency. This chapter provides an overview of the relevant studies conducted to identify the cell of origin of hepatocellular carcinoma with a special focus on the controversy of hepatocytes versus hepatic progenitors as the main tumor-initiating cell. Furthermore, we introduce the concept of cancer stem cells (CSCs) and highlight recent publications covering this topic in relation to liver cancer. More precisely, we concentrate on the origin of CSCs, discuss accepted markers and the need to define a consistent combination of them that can be utilized to clearly define this heterogeneous cell type, summarize important signaling pathways that govern the stemness, and describe state-of-the-art assays to isolate and evaluate CSCs. We focus on their contributions to oncogenesis and tumor heterogeneity, as well as their feature to resist chemo-and radiotherapy. Finally, the potential of using CSC markers for diagnostic purposes and therapeutic approaches targeting these cells is addressed.

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“…CD44(+) and CD133(+) were correlated with an enhanced AFP level as well as the risk of poorly differentiated HCC. CD44 or CD133 alone and in combination with microvascular invasion was independently associated with increased recurrence and poor prognosis of HCC patients [ 41 ]. The CD13 is another marker of CSCs.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cells of hepatocellular carcinoma

Wang

Sun

2018

Oncotarget

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Hepatocellular carcinoma is a malignant tumor arising from hepatocytes. The hepatocellular carcinoma is dictated by a subset of cells with stem cell-like features. These cells are apoptosis-resistant and have particular biomarkers, which serve as seeds in different stages of tumorigenesis including initiation, progression, metastasis, and relapse of hepatocellular carcinoma. Signaling pathways of cancer stem cells are novel targets for the radical intervention of hepatocellular carcinoma.

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Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma

Cited by 18 publications

References 28 publications

Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells

Ursolic acid inhibits proliferation and induces apoptosis by inactivating Wnt/β-catenin signaling in human osteosarcoma cells

Cellular Origin of Hepatocellular Carcinoma

Cancer stem cells of hepatocellular carcinoma

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