New cell surface markers for murine fetal hepatic stem cells identified through high density complementary DNA microarrays

Nierhoff, Dirk; LeVoci, Lauretta; Schulte, Sigrid; Goeser, Tobias; Rogler, Leslie E.; Shafritz, David A.

doi:10.1002/hep.21721

Cited by 41 publications

(43 citation statements)

References 39 publications

(51 reference statements)

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“…Recently, we have identified Nope as a new cell surface marker for murine fetal liver stem/progenitor cells. 15 In our present study, we detected high expression levels of Nope in all HCC samples obtained from an oncogenic mouse model as well as in the murine hepatoma cell line Hepa 1-6 on mRNA and protein level. Nope expression was selectively detected in all analyzed HCC specimens but not in normal liver or dysplastic lesions and high induction of Nope expression started at the initial time point when preneoplastic lesions transform to malignant HCC.…”

Section: Early Detection and Diagnosissupporting

confidence: 61%

“…The detected bands separated consistent with a different glycosylation status of unknown functional relevance as previously described and were identical to those with protein extract of murine fetal liver that was used as positive control. 15 Also, Western Blot analysis for Nope displayed a much stronger expression pattern in membranous protein enriched fractions, as compared to total protein fractions (Fig. 1b).…”

Section: Nope Expression In Murine Hepatoma Cell Linesmentioning

confidence: 84%

“…15 In analogy to commonly used HCC markers such as Afp and Gpc-3, we here establish Nope as a novel oncofetal surface marker for murine and human HCC.…”

mentioning

confidence: 98%

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Neighbor of punc E11, a novel oncofetal marker for hepatocellular carcinoma

Marquardt

Quasdorff

Varnholt

et al. 2010

Intl Journal of Cancer

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Hepatocellular carcinoma (HCC) is the 5th common malignancy worldwide, but established markers fail to detect up to one third of HCC. We have recently identified Neighbor of Punc E11 (Nope) as a surface marker for murine fetal liver stem cells. Similar to commonly used HCC markers such as a-Fetoprotein (Afp) and Glypican-3 (Gpc-3), we here establish Nope as an oncofetal marker of murine and human HCC and investigate its specific expression in hepatoma cell lines and primary HCC. Murine and human hepatoma cell lines and Cre-inducible SV40 T-antigen transgenic mice (Alb-SV40TAg ind ) were analyzed for Nope expression in comparison to common HCC markers by quantitative RT-PCR, Western blot analyses and immunohistochemistry. Nope expression in primary human HCC was investigated using Oncomine Microarray database. Nope expression was elevated in 8 of 10 investigated murine and human hepatoma cell lines and in all tumors of our oncogenic mouse model but remained undetectable in normal liver and at preneoplastic stages of murine hepatocarcinogenesis. Furthermore, a significant induction of Nope was detected in primary human cancers compared to corresponding normal or cirrhotic tissue. Nope expression in tumor specimens and murine cell lines correlated closely with expression levels of Gpc-3, whereas expression levels of Afp showed high variations. In conclusion, we identified Nope as a novel oncofetal surface marker for murine and human HCC. Nope is specifically expressed by epithelial tumor cells but not in preneoplastic stages and is a promising marker for clinical application because of its high detection rate in Afp-positive and Afp-negative tumors.Hepatocellular carcinoma (HCC) is the 5th common malignancy worldwide. The incidence in developed countries has almost doubled within the last 40 years and remains constantly increasing.1-4 The high mortality of HCC ranks it among the most common cause of cancer-related deaths together with colon and lung cancer. Although many novel therapeutic strategies have been developed in the past, the 5-year survival rate remains poor with approximately 5%.3 Because of the late diagnosis, more than 40% of the patients cannot be treated in a curative intention.5 Thus, early detection is considered the most important prognostic factor for survival.Clinically established screening methods for HCC such as ultrasound and elevated serum levels of a-fetoprotein (AFP) slightly improved the prognosis, but sensitivity and specificity are still limited especially in early stages of tumor development.6-8 Moreover, clinically established tumor markers fail to detect up to one third of HCC completely. Apart from high sensitivity and reliable detection of early stages in carcinogenesis, limited expression in normal tissue and independency of the underlying disease and its stage are further attributes of ideal tumor markers. Apart from AFP, other biomarkers (AFP-L3, Golgi protein 73, des-y-carboxy prothrombin (DCP) and Glypican-3 (GPC-3)) have been identified, and some show promising results for ...

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Section: Early Detection and Diagnosissupporting

confidence: 61%

Section: Nope Expression In Murine Hepatoma Cell Linesmentioning

confidence: 84%

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Neighbor of punc E11, a novel oncofetal marker for hepatocellular carcinoma

Marquardt

Quasdorff

Varnholt

et al. 2010

Intl Journal of Cancer

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“…E-cadherin and LIV2 are also useful epithelial-speciic markers to isolate epithelial cells expressed in the E12.5 mouse liver [13][14][15][16]. CD24a and neighbor of Punc E11 (NOPE) were also identiied as sorting markers [17]. HNF4α+ liver stem/progenitor cells express epithelial cell adhesion molecule (EpCAM) in mice as early as E9.5.…”

Section: Fetal Liver Stem/progenitor Cellsmentioning

confidence: 99%

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

Tomita¹,

Kanayama²,

Niwa³

et al. 2017

Updates in Liver Cancer

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The cancer stem cell (CSC) theory posits that a small population of cells with stem celllike features is responsible for tumor growth, resistance, and recurrence in many malignancies. This theory could be a useful paradigm for designing innovative targeted drug therapies. Liver cancer is the ifth most common cancer worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) as the predominant forms. Hepatic stem/progenitor cells are believed to be the origin of HCCs and CCAs; however, this remains a controversial topic. Aldehyde dehydrogenase (ALDH) is the main enzymatic system responsible for the clearance of acetaldehyde from the hepatocytes in the liver tissue. Therefore, ALDH1 has been suggested to be a potential, biological and CSC marker in liver cancers. We here provide an overview of the current state of knowledge of CSCs in liver and the role of ALDH1 in the development and progression of liver cancers and discuss its potential value as a prognostic and diagnostic biomarker.

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“…These findings make the isolation of liver progenitors easier. However, the number of OCs in the normal liver is extremely low; therefore, many researchers have characterized the hepatoblasts from fetal liver (Dan et al, 2006;Nierhoff et al, 2007 (Dan et al, 2006). A third source is exogenous stem cells, which may be derived from bone marrow (BM) or other organs or tissues.…”

Section: Hepatic Stem Cells: Extrinsic and Intrinsic Sourcesmentioning

confidence: 99%

Stem cell plasticity: Learning from hepatogenic differentiation strategies

Banas¹,

Yamamoto

Teratani³

et al. 2007

Developmental Dynamics

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Many studies on stem cell plasticity are challenging the concept that stem cells contain an intrinsically predefined, unidirectional differentiation program. This means that the developmental fate of a stem cell is dependent on the general potential of the cell (pre-determined stem cell fate) as well as on microenvironmental cues, such as stimuli from growth factors (stem cell niche). Here, we reviewed reports that examined the hepatocyte differentiation ability of stem cells from two different sources: embryonic stem cells and adult stem cells. All of those stem cells revealed the ability to give rise to hepatocyte-like cells using different induction strategies. However, it is still not clear which of those stem cells would be the best source for hepatocyte replacement or which would be the best protocol. We herein present the current knowledge regarding available protocols and factors used in order to obtain functional hepatocytes from stem cells. Developmental Dynamics 236:3228 -3241, 2007.

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New cell surface markers for murine fetal hepatic stem cells identified through high density complementary DNA microarrays

Cited by 41 publications

References 39 publications

Neighbor of punc E11, a novel oncofetal marker for hepatocellular carcinoma

Neighbor of punc E11, a novel oncofetal marker for hepatocellular carcinoma

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

Stem cell plasticity: Learning from hepatogenic differentiation strategies

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