Occurrence of c-kit+ Tumor Cells in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Lee, Eung Seok; Han, Eun Mee; Kim, Young‐Sik; Shin, Bong Kyung; Kim, Chul‐Hwan; Kim, Han Kyeom; Won, Nam Hee; Yeom, Bom Woo; Kim, Insun

doi:10.1309/lett-wn3l-uf51-6hr0

Cited by 16 publications

(19 citation statements)

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“…Recently, Thy-1 has been shown to be decisive for tumorigenicity of HCC cell lines, and although the overall expression of this marker is usually <1% (24) it was proposed as a novel marker for diagnosis and treatment of human HCC (25). Notably, expression of c-kit was linked to Hepatitis B virus infection, which is mirrored by the higher expression in Hep3B and Huh-7 in our setting, which were established on the basis of viral hepatitis (26,27). …”

Section: Discussionmentioning

confidence: 78%

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Jabari

Meissnitzer²,

Quint³

et al. 2009

Int J Oncol

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Abstract. Tumor cells have the capability to trans-and to dedifferentiate, for example by reactivating embryonic development genes and stem cell characteristics. The aim of our study was to show the differential expression of stem-and progenitor cell markers in human hepatocellular carcinoma cell lines (HCC). Different human HCC cell lines (HUH7, HUH7 5-15, HUH7 pcDNA3.1, Hep3B and HepG2) were cultured under standard conditions in vitro or implanted subcutaneously (5x10 6 cells) in male NMRI mice. Specimens were characterized by quantitative real-time PCR, Western blotting, methylation-specific PCR and immunohistochemistry for markers of differentiation (cytokeratins, vimentin), embryonic development or stem cells (PTC, PDX-1, SHH, Thy1, c-kit, CD34, ß-catenin, Ki-67). The investigated HCC cell lines showed different patterns of marker expression allowing to distinguish four distinct groups: the classical cholangiocellular type (Huh-7, Huh-7 pcDNA3.1, Hep3B) with expression of CK7/19, ß-catenin and CD34; a dedifferentiated mesenchymal-proliferative type (Huh-7 5-15) characterized by CK19, Vimentin and Ki-67; a dedifferentiated embryonic-development type (Hep3B implanted in matrigel) with expression of CK19, ß-catenin and PTC and a classical HCC type (HepG2) showing CK18/19 and ß-catenin expression. HCC cell lines showed significantly different expression patterns of differentiation markers in a xenograft model. Furthermore, direct association of some markers was observed. The groups differ from each other in expression patterns, but also show that environmental factors play an important role in the behaviour of cells.

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Section: Discussionmentioning

confidence: 78%

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Jabari

Meissnitzer²,

Quint³

et al. 2009

Int J Oncol

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“…As mentioned in the literature, in prepared specimens, oval round cells stained with c-Kit were evaluated in the present study. Lee et al (8) stated that expression of c-Kit is also noted in mast cells with a distinctive membranous pattern of staining. In addition to morphological differences, leukocyte common antigen (CD45) immunostaining in consecutive sections allowed the separation of mast cells from c-Kit positive progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

“…These oval cells are bipotential and have the ability to differentiate into either hepatocytes or biliary epithelial cells. c-Kit is considered to be a determinant marker for these cells (8). In addi-tion, it has also been reported in several studies that oval cells may be the progenitor cells of HCC and cholangiocarcinoma (8)(9)(10).…”

Section: Introductionmentioning

confidence: 95%

Can the Presence of C-Kit-Positive Hepatic Progenitor Cells in Chronic Hepatitis C Have a Role in the Follow-Up of the Disease?

Koruk¹,

Özardalı²,

Dıncoglu³

et al. 2012

Erciyes Med J

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ÖZETObjective: The aim of this study was to compare the clinical and pathological properties of cases of hepatitis C virus (HCV) infection with respect to the presence or absence of hepatic progenitor cells positive for the proto-oncogene c-Kit (CD117) in hepatic tissue. Material and Methods:The study was performed on hepatic biopsy specimens from 61 cases with HCV infection. Stained hepatic biopsy slides were examined. Immunohistochemical staining was performed using an anti-c-Kit antibody. The cases were divided into four groups (minimal, mild, moderate and severe according to their total hepatic activity index and into two groups (none/mild, moderate/severe) according to fibrosis grade.Results: c-Kit-positive oval cells were detected in 30 cases (49.1%). There was no statistically significant difference in cKit positivity status with respect to the ALT, AST or HCV RNA results. c-Kit positivity increased with increasing hepatitis grade (p<0.001). In cases with moderate/severe fibrosis, c-Kit positivity was found to be higher than in cases with no fibrosis or low-grade fibrosis (p<0.02). Conclusion:It was found that HCV patients with more inflammation and fibrosis were more likely to present c-Kit-positive hepatic progenitor cells. c-Kit expression in hepatic progenitor cells could possibly be used in the follow-up of patients with HCV. Larger patient cohorts are needed to confirm these results.

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“…Oval cells are involved in the pathogenesis of hepatocellular carcinoma (HCC) (5,15). The expression of the hematopoietic markers by oval cells may be of biologic significance, especially the c-Kit, which had been suggested to playing critical functions in regulating hematopoietic cell proliferation, migration and carcinogenesis (16).…”

Section: Discussionmentioning

confidence: 99%

Blocking SCF/c‐Kit signal did not inhibit the proliferation of cultured liver progenitor cells

Jin

et al. 2007

IUBMB Life

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SummaryOval cells are the putative liver stem cells that proliferate during hepatocarcinogenesis and chemically-induced severe liver injury. Antigens traditionally associated with haematopoietic cells, such as c-Kit, have been reported to be expressed by oval cells. Previous studies suggested that stem cell factor (SCF) and c-Kit were critical to oval cell development. However, the role of SCF/c-Kit signals in oval cell proliferation still remains unclear. Recently, we reported the establishment of oval cell-derived liver epithelial progenitor cells (LEPCs). In this work, we showed LEPCs co-expressed c-Kit and its ligand SCF. The involvement of SCF/c-Kit signals in LEPCs proliferation was investigated either by exposing LEPCs to c-Kit inhibitors (STI571 and AG1296), SCF, anti-SCF neutralized antibody or by using small interfering RNA to knock-down c-Kit expression. Our data demonstrate that blocking SCF/c-Kit signal did not inhibit the proliferation of LEPCs, which suggest SCF/c-Kit is not necessary for the proliferation of oval cells, at least for the cultured oval cell counterpart LEPCs. IUBMB Life, 59: 458-464, 2007

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Occurrence of c-kit+ Tumor Cells in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Cited by 16 publications

References 0 publications

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Cellular plasticity of trans- and dedifferentiation markers in human hepatoma cells in vitro and in vivo

Can the Presence of C-Kit-Positive Hepatic Progenitor Cells in Chronic Hepatitis C Have a Role in the Follow-Up of the Disease?

Blocking SCF/c‐Kit signal did not inhibit the proliferation of cultured liver progenitor cells

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