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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The "in vitro" establishment of a physiological model of bipotential liver progenitors would be useful for analyzing the molecular mechanisms involved in regulating growth and differentiation, as well as studying their potential role/s in liver physiology and pathology. The transforming growth factor-beta (TGF-beta) induces de-differentiation of fetal rat hepatocytes (FH), concomitant with changes in morphology. The aim of this work was to isolate and characterize this population of TGF-beta-treated fetal hepatocytes (TbetaT-FH) and test whether they can behave as liver progenitors. The TbetaT-FH isolated cell lines show high expression of Thy-1 and low expression of c-Kit. They express liver-specific proteins, such as albumin and alpha-fetoprotein, and mesenchymal markers, such as vimentin. TbetaT-FH maintain expression of the hnf3beta gene, but lose expression of hnf1beta, hnf4, and hnf6. They express c-met and show an increase in proliferation in response to HGF. Interestingly, the transdifferentiation process is coincident with changes in the expression of genes related to the oxidative metabolism. TbetaT-FH cultured in the presence of EGF + DMSO change morphology, towards epithelial cells, gaining expression of CK19 and c-Kit, markers found in hepatoblasts and bile duct cells. Furthermore, TbetaT-FH form duct-like structures when cultured on Matrigel. TbetaT-FH show also potential to revert to an hepatocyte phenotype when submitted to a long-term "in vitro" differentiation protocol towards hepatocytic lineage. In summary, our results support the hypothesis that hepatocytes can function as facultative liver stem cells and demonstrate that TGF-beta might play an essential role in the transdifferentiation process.
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PMID:Isolation and characterization of a putative liver progenitor population after treatment of fetal rat hepatocytes with TGF-beta. 1828 37

The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. Recently, we have identified that a hepatic stem cell marker, epithelial cell adhesion molecule (EpCAM), may serve as an early biomarker of HCC because its expression is highly elevated in premalignant hepatic tissues and in a subset of HCC. In this study, we aimed to identify novel HCC subtypes that resemble certain stages of liver lineages by searching for EpCAM-coexpressed genes. A unique signature of EpCAM-positive HCCs was identified by cDNA microarray analysis of 40 HCC cases and validated by oligonucleotide microarray analysis of 238 independent HCC cases, which was further confirmed by immunohistochemical analysis of an additional 101 HCC cases. EpCAM-positive HCC displayed a distinct molecular signature with features of hepatic progenitor cells including the presence of known stem/progenitor markers such as cytokeratin 19, c-Kit, EpCAM, and activated Wnt-beta-catenin signaling, whereas EpCAM-negative HCC displayed genes with features of mature hepatocytes. Moreover, EpCAM-positive and EpCAM-negative HCC could be further subclassified into four groups with prognostic implication by determining the level of alpha-fetoprotein (AFP). These four subtypes displayed distinct gene expression patterns with features resembling certain stages of hepatic lineages. Taken together, we proposed an easy classification system defined by EpCAM and AFP to reveal HCC subtypes similar to hepatic cell maturation lineages, which may enable prognostic stratification and assessment of HCC patients with adjuvant therapy and provide new insights into the potential cellular origin of HCC and its activated molecular pathways.
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PMID:EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. 1831 9

Intra cranial germ cell tumors (GCTs) usually arise in midline structures, including the pineal or suprasellar regions of children and young adults. The classification of GCTs includes germinoma, teratoma, yolk sac tumor, embryonal carcinoma, and choriocarcinoma. However, intracranial GCTs are often of mixed histologic composition (mixed GCTs), and only germinoma and teratoma are likely to be encountered as pure tumor types. Although GCTs are usually identified using conventional histological techniques, immunohistochemical studies are very useful for delineating these entities, using special markers such as human chorionic gonadotropin, alpha-fetoprotein, human placental alkaline phosphatase, cytokeratin, as well as c-kit and OCT4. Ultrastructural examination is also useful in confirming the identity of these tumors. Genetic alterations specifically encountered in central nervous system GCTs are largely unknown. Patients with Klinefelter syndrome or Down syndrome appear to be predisposed to the development of gonadal as well as intracranial germinomas. Frequent imbalances of chromosomes have been described in intracranial GCTs, including chromosomes 1, 8, 12, 13, 18 and X. Recently, p14 and c-kit gene alterations have been reported, particularly in some intracranial germinomas; however, their importance remains unclear.
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PMID:Pathology of intracranial germ cell tumors. 1932 61

Novel human embryonal stem cell lines C612 and C910 have been established from hatching blastocytes. Cells were cultivated in mTeST medium on mouse fibroblast feeder-layers. They express common pluripotent markers such as alkaline phosphatase, Oct 3/4, SEEA-4, Nanog, Rex1. Immunophenotyping of these cells by flow cytometry revealed expression of CD90 (Thy-1) and CD117 (c-kit) antigens and weak or no expression of CD13, CD34, CD45, CD130, HLA class I and HLA class II antigens. This pattern of surface antigen expression is common for human embryonic stem cells. G-banding assay of C612 and C910 metaphase plates showed that karyotypic structure of these cells was normal both in chromosome number and structure. The cells are pluripotent because of their capability to generate embryoid bodies, undergo spontaneous differentiation and express markers of all germ layers: nestin, keratin, vimentin (ectoderm), alpha-fetoprotein (entoderm), and muscle alpha-actinin (mesoderm). Thus, C612 and C910 cells have all attributes of typical human embryonic stem cells (diploid, capable of self-renewal, express pluripotent markers and differentiate into three germ layers) and may be of potential use for fundamental and regenerative medicine researches.
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PMID:[Novel human embryonic stem cell lines C612 and C910]. 1976 46

We investigated the role of the hematopoietically expressed homeobox (Hex) in the differentiation and development of hepatocytes within embryonic stem cell (ESC)-derived embryoid bodies (EBs). Analyses of hepatic endoderm derived from Hex(-/-) EBs revealed a dramatic reduction in the levels of albumin (Alb) and alpha-fetoprotein (Afp) expression. In contrast, stage-specific forced expression of Hex in EBs from wild-type ESCs led to the up-regulation of Alb and Afp expression and secretion of Alb and transferrin. These inductive effects were restricted to c-kit(+) endoderm-enriched EB-derived populations, suggesting that Hex functions at the level of hepatic specification of endoderm in this model. Microarray analysis revealed that Hex regulated the expression of a broad spectrum of hepatocyte-related genes, including fibrinogens, apolipoproteins, and cytochromes. When added to the endoderm-induced EBs, bone morphogenetic protein 4 acted synergistically with Hex in the induction of expression of Alb, Afp, carbamoyl phosphate synthetase, transcription factor 1, and CCAAT/enhancer binding protein alpha. These findings indicate that Hex plays a pivotal role during induction of liver development from endoderm in this in vitro model and suggest that this strategy may provide important insight into the generation of functional hepatocytes from ESCs.
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PMID:The homeobox gene Hex regulates hepatocyte differentiation from embryonic stem cell-derived endoderm. 2006 80

Cell therapy represents the most promising alternative strategy for end-stage liver diseases and hepatic progenitors are the best candidates. We have identified a reservoir of immature hepatic precursors within human cord blood, which can derive engraftable bipotent progenitors. We isolated a stem cell subset CD133+/CD34+/OV6(low) expressing a surface-marker profile consistent with that of fetal liver cells. Upon induction of hepatic commitment by a medium containing cytokines and factors involved in vivo oval-cell activation, a heterogeneous cell population displaying characteristics of functional oval-cell-like bipotent hepatic progenitors was obtained. The cells expressed markers of hepatocytes and cholangiocytes and were highly enriched in OV6, c-Met, c-Kit, and Thy-1. They also displayed liver functional activity as glycogen storage, urea production, albumin secretion, and inducible CyP2B6 activity. When injected into liver-damaged severe-combined immunodeficient mice, induced bipotent hepatic progenitors appropriately engrafted livers of recipient animals, where they formed clusters of human-derived cells expressing human leucocyte antigen-class I, Hep-Par1, and OV6 antigens. Human-specific albumin, alpha-fetoprotein, and cytokeratin 19 were also expressed. In transplanted animals, AST serum levels showed a significative reduction with regard to controls. This human model for in vitro progenitor-cell activation may provide a powerful tool for elucidating the pathways and synergies that regulate this complex process and can represent a valuable source, exploitable for liver cell-based therapies and regenerative medicine.
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PMID:Cord blood CD133 cells define an OV6-positive population that can be differentiated in vitro into engraftable bipotent hepatic progenitors. 2129 16

Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.
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PMID:Clinicopathologic study on combined hepatocellular carcinoma and cholangiocarcinoma: with emphasis on the intermediate cell morphology. 2186 May 52

Cancer stem cells (CSCs) have been observed to share certain characteristics with normal stem cells. It was an important argument for cancer therapy and a successful progenitor inhibition could show us targeted cell type for a novel strategy. In this study, we aimed to constitute an inhibition in different stages of hepatic stem/progenitor cells (HPCs) with verapamil. Expression patterns of alpha-fetoprotein (AFP), c-kit (CD117) and p-glycoprotein were investigated in developing mouse on the embryonic day (E) 15, E18 and E21 to characterize early and late stages of HPCs. Proliferation inhibition with 5-Bromo-2-Deoxyuridin (BrdU) incorporation and maturation inhibition with PAS staining results were supported by morphometrical analysis during these periods. AFP, c-kit and p-glycoprotein immunoreactivity increased especially in E15 but decreased in E18 and E21 of the control groups during embryonic development. Verapamil treatment effected particularly E15 cells and immunoexpression of HPCs significantly decreased. Proliferation inhibition was observed in all embryonic days of mouse with verapamil and this drug inhibited not only maturation of HPCs in E18 and E21 embryos, but also decreased HPC number in the same embryonic period. According to our results, we estimated that similar to the early and late progenitor stages of HPCs, CSCc can also be in different stages in a heterogenic tumour bulk and the difficulty of CSC inhibition could be the main mechanism of tumour relapses. In this study, HPCs inhibition by verapamil in E15 was not observed in E18 and E21. As similar, CSCs treatments targeting different stages may be impotent to cells in tumour initiating cell stage. We can speculate that ineffectiveness of CSC-specific therapies may be attributed to the highly selective specificity of the treatment (Fig. 6, Ref. 28).
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PMID:Hepatic progenitor cell inhibition during embryonic period with high dose verapamil; liable joint to the cancer therapy. 2382 19

The patient was a 43-year-old man with chronic hepatitis B without history of hepatocellular carcinoma (HCC), who was first diagnosed with thrombosis in right portal vein trunk and portal vein branches and ruptured esophageal varices in October 2011. He underwent endoscopic variceal ligation, but ruptured repeatedly. Despite anti-coagulant therapy, the thrombosis expanded from right portal vein trunk to upper mesenteric vein in March 2012. Computed tomography (CT) scan showed that portal vein thrombosis had low density from early to late phase. No focal liver lesions were identified by CT scan or ultrasound, and alpha-fetoprotein (AFP) was within normal range. He died by intractable esophageal variceal bleeding in April 2012. Pathological examination of autopsy specimen showed that portal vein thrombosis was consistent with poorly-differentiated HCC. The portal vein tumor thrombosis (PVTT) had only a few tumor vessels, which were compressed by fibromatous change originating from HCC formation, so were represented as low-density lesions from arterial to portal phase of CT. In addition, PVTT was negative for AFP, so representing serum value of AFP within normal range. PVTT had positive staining for c-kit, which is a liver stem cell marker. Liver tumors in the whole liver parenchyma were not found pathologically. PVTT might have the characteristics of presumed liver cancer stem cells. We experienced the first case of HCC only in portal vein without liver parenchyma tumor nodules, with difficult differential diagnosis from a non-malignant portal vein thrombosis. We also reported new tumor profiles of the portal venous tumor growth- type of HCC.
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PMID:Portal venous tumor growth-type of hepatocellular carcinoma without liver parenchyma tumor nodules: a case report. 2411 29

Mouse submandibular salivary gland cells and liver progenitor cells from long-term in vitro cultures with a high proliferation potential were side-by-side compared by methods of immunocytochemistry, quantitative real-time PCR, flow cytometry, and transcriptome analysis. The two cell types were found to be similar in expressing cell markers such as EpCAM, CD29, c-Kit, Sca-1, and c-Met. In addition, both cell types expressed cytokeratins 8, 18, and 19, alpha-fetoprotein, and (weakly) albumin. Unlike the liver cells, however, the salivary gland cells in culture showed high-level expression of cytokeratin 14 and CD49f, which was indicative of their origin from salivary gland ducts. Quantitative real-time PCR and deep-sequencing transcriptome analysis revealed similarities in the expression pattern of transcription factors between the two cell types. In this respect, however, the cultured salivary gland cells proved to be closer to exocrine cells of the pancreas than to the liver progenitor cells. Thus, ductal cells of postnatal submandibular salivary glands in culture show phenotypic convergence with progenitor cells of endodermal origin, suggesting that these glands may serve as a potential cell source for cellular therapy of hepatic and pancreatic disorders. The results of this study provide a deeper insight into the molecular features of salivary gland cells and may help optimize procedures for stimulating their differentiation in a specified direction.
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PMID:Comparative analysis reveals similarities between cultured submandibular salivary gland cells and liver progenitor cells. 2479 Aug 27


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