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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of E- and P-cadherin in 24 primary hepatocellular carcinomas, together with the non-cancerous liver tissue from each case, was examined by immunohistochemical staining. Cells of 23 grade I-III carcinomas as well as hepatocytes in all the non-cancerous livers expressed E-cadherin at the cell-cell boundary and showed tight intercellular adhesion without exception. However, a highly undifferentiated carcinoma classified as grade IV apparently lacked E-cadherin expression and also showed decreased intercellular adhesiveness. Loss of E-cadherin expression may be one of the characteristics of highly undifferentiated hepatocellular carcinoma. In contrast to E-cadherin, P-cadherin was never detected in either the cancer cells or non-cancerous hepatocytes in all cases.
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PMID:Cadherin intercellular adhesion molecule in hepatocellular carcinomas: loss of E-cadherin expression in an undifferentiated carcinoma. 185 Oct 53

The expression of connexin 32, a major gap junction protein, and E-cadherin, an intercellular adhesion molecule that is supposed to be involved in the regulation of gap junctional intercellular communications, was examined immunohistochemically in seven specimens of human hepatocellular carcinoma and surrounding non-carcinomatous tissues. We found that the number of connexin 32-positive spots per mm2 was significantly less in hepatocellular carcinoma tissues than in the surrounding non-carcinomatous cirrhotic tissues (4360 +/- 3390/mm2 vs 10,030 +/- 3690/mm2; p < 0.01). The number in the latter was also significantly less than that in normal controls (23,560 +/- 4170/mm2). E-cadherin was expressed in all non-carcinomatous hepatocytes as well as carcinomatous cells, except for one case of Edmondson's grade III hepatocellular carcinoma. These results suggest an impairment of cell-to-cell communications in human hepatocellular carcinomas.
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PMID:Expression of gap junction protein connexin 32 and E-cadherin in human hepatocellular carcinoma. 765 Mar 33

By immunofluorescence and freeze fracture methods, we have studied the establishment of hepatic cell polarity in WIF-B9 cells, a subclone of the WIF-B rat hepatoma-derived hybrid cell line. As previously shown (Ihrke et al. (1993) J. Cell Biol. 123, 1761-1775; Shanks et al. (1994) J. Cell Sci. 107, 813-825), these cells are a suitable model for in vitro studies of various hepatic functions, particularly polarity: in confluent cultures, the majority of cells form bile canaliculus-like structures; membrane domains are settled, according to plasma membrane protein localization similar to rat hepatocytes in situ. We here report that the establishment of WIF-B9 cell polarity is a slow progressive biphasic phenomenon. During the first days of culture, the majority of cells do not make bile canaliculus-like structures. However, they display a polarity similar to that of simple epithelial cells: apical membrane proteins and villin are found at the cell apex; basolateral ones, excluded from this area, are expressed in the remaining membrane area; the tight junction-associated protein ZO-1 and actin are concentrated at the boundary of these two poles, whereas E-cadherin is present at the lateral pole just under the apex. With time in culture, the number of cells expressing this simple epithelial polarized phenotype decreases progressively and, after 10-15 days, depending on the plating density, nearly all the cells express the typical hepatic polarized phenotype. The expression of these two phenotypes is mutually exclusive. Freeze-fracture replicas of both types of polarized cells show either macula occludens, fascia occludens (simple epithelial polarity) or zonula occludens (hepatic polarity), associated with gap junctions. In this last case, two or three continuous strands are generally present all around the bile canaliculus-like structures.
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PMID:Establishment of hepatic cell polarity in the rat hepatoma-human fibroblast hybrid WIF-B9. A biphasic phenomenon going from a simple epithelial polarized phenotype to an hepatic polarized one. 879 49

We have analyzed the composition of the tumor stroma and the expression of cell-matrix and cell-cell adhesion molecules in 11 cases of fibrolamellar carcinoma of the liver (FLC), in comparison with 34 cases of hepatocellular carcinoma and 8 cases of focal nodular hyperplasia. Fibrolamellar carcinoma was characterized by the presence of large amounts of tenascin in tumor stroma and by the scarce expression of basement membrane components at the contact of neoplastic clusters. Like normal hepatocytes, neoplastic cells constantly expressed the alpha1 integrin chain, lacked the beta4 integrin chain, and coexpressed E-cadherin and the hepatocyte N-related cadherin. Abnormalities in the expression of cell adhesion molecules, including altered cadherin expression, alphaV integrin chain induction, and CD44 expression, were detected in the majority of cases. The composition of the tumor stroma and the pattern of expression of cell adhesion molecules in fibrolamellar carcinoma were reminiscent of those observed in grade III and grade IV hepatocellular carcinomas. Our results therefore show that, despite its slow local growth and good prognosis, fibrolamellar carcinoma expresses many characteristics usually associated with clinically aggressive malignancies. Further studies are needed to identify the factors responsible for the apparent dissociation between clinical behavior and biological characteristics in this tumor.
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PMID:Fibrolamellar carcinoma of the liver: composition of the extracellular matrix and expression of cell-matrix and cell-cell adhesion molecules. 890 87

In human hepatocellular carcinoma (HCC), the liver is the major target organ of metastasis, which is known as intrahepatic metastasis. To analyze the mechanism of this metastasis, we established two sublines from the human HCC cell line Li7. Subline Li7HM produced multiple liver metastasis, whereas subline Li7NM never did so after intrasplenic injection into nude mice. Two-dimensional gel electrophoresis and immunoblot analysis showed that only Li7NM expressed vimentin and lacked E-cadherin expression, indicating that this clone had undergone epithelial-mesenchymal transition. We then transfected mouse E-cadherin complementary DNA into Li7NM cells and found that the transfectant cells (EM16.21B.3) formed liver metastasis (8/16 mice) after intrasplenic injection and liver tumors (11/13 mice) after intrahepatic injection, whereas the control cell line formed no tumors. These results suggest that E-cadherin plays an important role in the process of intrahepatic metastasis of HCC.
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PMID:E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma. 893 81

Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology.
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PMID:The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas. 913 67

We have recently shown that stable expression of an epitope-tagged cDNA of the hepatocyte- enriched transcription factor, hepatocyte nuclear factor (HNF)4, in dedifferentiated rat hepatoma H5 cells is sufficient to provoke reexpression of a set of hepatocyte marker genes. Here, we demonstrate that the effects of HNF4 expression extend to the reestablishment of differentiated epithelial cell morphology and simple epithelial polarity. The acquisition of epithelial morphology occurs in two steps. First, expression of HNF4 results in reexpression of cytokeratin proteins and partial reestablishment of E-cadherin production. Only the transfectants are competent to respond to the synthetic glucocorticoid dexamethasone, which induces the second step of morphogenesis, including formation of the junctional complex and expression of a polarized cell phenotype. Cell fusion experiments revealed that the transfectant cells, which show only partial restoration of E-cadherin expression, produce an extinguisher that is capable of acting in trans to downregulate the E-cadherin gene of well-differentiated hepatoma cells. Bypass of this repression by stable expression of E-cadherin in H5 cells is sufficient to establish some epithelial cell characteristics, implying that the morphogenic potential of HNF4 in hepatic cells acts via activation of the E-cadherin gene. Thus, HNF4 seems to integrate the genetic programs of liver-specific gene expression and epithelial morphogenesis.
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PMID:Hepatocyte nuclear factor 4 provokes expression of epithelial marker genes, acting as a morphogen in dedifferentiated hepatoma cells. 947 44

In the present retrospective study, liver cell dysplasia (LCD) occurring in cirrhotic livers associated or not associated with hepatocellular carcinoma (HCC) was immunohistochemically analyzed for the expression of hepatocyte growth factor receptor (c-met protein), Rb (retinoblastoma gene) protein, E-cadherin, and transforming growth factor-beta-1 (TGF-beta-1). Cytoplasmic c-met protein staining was observed in about half of the HCC's, and its prevalence was about twice as high in high grade vs. low grade tumors, but it was not correlated with proliferative activity as based on PCNA labelling. In LCD, reactivity for c-met protein was restricted to the small cell type. Nuclear staining for Rb protein was found in HCC's, and was not related to type, grade or proliferative activity, whereas no immunoreactivity was observed in normal, hyperplastic or dysplastic hepatocytes. Expression of E-cadherin prevailed in HCC's of lower grade, and particularly in those with a trabecular or acinar growth pattern. E-cadherin staining was detectable in normal and large dysplastic hepatocytes, but not in small dysplastic liver cells. TGF-beta-1 reactivity was observed in more than half the HCC's, but not in normal or dysplastic hepatocytes. These findings underline the phenotypic difference between large cell and small cell liver dysplasia, and support the hypothesis that small cell dysplasia is a precursor lesion in a hepatocarcinogenic pathway.
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PMID:Liver cell dysplasia: reactivities for c-met protein, Rb protein, E-cadherin and transforming growth factor-beta 1 in comparison with hepatocellular carcinoma. 969 Jan 21

We have studied two aspects of the plasma membrane of hepatocytes, highly differentiated epithelial cells that exhibit a particular and complex polarity. Using a genetic approach, we have distinguished between the expression/regulation of proteins specific for all three hepatocyte membrane domains and their organization into discrete domains. For this analysis we used a panel of previously isolated cell clones, derived from the differentiated rat hepatoma line H4IIEC3, and that present different expression patterns for liver-specific genes. This panel was composed of (1) differentiated clones, (2) chromosomally reduced hepatoma-fibroblast hybrids characterized by a pleiotropic extinction/reexpression of liver-specific genes and (3) dedifferentiated variant and revertant clones. The expression of 16 hepatocyte membrane polarity markers was studied by western blotting and immunolocalization. Even though cells of differentiated clones express all of these polarity markers, they are not polarized, and are therefore suitable for studying the regulation of plasma membrane protein expression, and for identifying gene products implicated in the establishment of membrane polarity. In hepatoma-fibroblast hybrids the expression of four markers, three apical (dipeptidylpeptidase IV, alkaline phosphodiesterase B10 and polymeric IgA receptor) and one lateral (E-cadherin), is down-regulated in extinguished clones and restored in reexpressing subclones, as previously reported for liver-specific functions. The dipeptidylpeptidase IV mRNA was undetectable or strongly reduced in extinguished hybrids, but expressed at a robust level in some of the reexpressing clones. Concerning the dedifferentiated variants, each has its own pattern of membrane marker expression (loss of expression of three to six markers), that differs from that of extinguished hybrids. Revertant cells express all of the membrane markers examined. Among all of these hepatoma derivatives, only cells of reexpressing hybrids are polarized, and form bile canaliculi-like structures, with spherical and even, for one clone, long tubular and branched forms. All apical markers examined are confined in these canalicular structures, whereas the other markers are excluded from them, and present on the rest of the membrane (basolateral markers) or at the cell-cell contacts (lateral markers). Cells of reexpressing hybrids also express simple epithelial polarity. Thus the expression of only a few hepatocyte-domain-specific plasma membrane proteins is subject to down-regulation, as is the case for liver-specific genes so far studied, and the expression of polarity markers and the formation of poles are dissociable events.
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PMID:Expression and localization of hepatocyte domain-specific plasma membrane proteins in hepatoma x fibroblast hybrids and in hepatoma dedifferentiated variants. 978 84

This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, MCa-29, MCa-35, and MCa-K), ovarian carcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG. These tumors vary widely in their ability to spontaneously metastasize to the lung (from 0 to 100% metastatic incidence), and their cells greatly differ in their ability to form artificial lung nodules when injected i.v. Primary tumors in the leg were assessed for E-cadherin and beta-catenin expression by western blotting. The expression of both proteins showed wide variation among the tumors; however, the expression of E-cadherin correlated well with that of beta-catenin. There was significant inverse correlation between the expression of E-cadherin, as well as beta-catenin, and the incidence of both spontaneous and artificial lung metastases from these tumors. Spontaneous metastases of highly metastatic HCa-I and moderately metastatic MCa-35 were significantly lower in E-cadherin and beta-catenin expression than their corresponding primary tumors were. Thus, the propensity of murine carcinomas for hematogenous spread is highly related to E-cadherin and beta-catenin levels in primary tumors. The inverse correlation between the expression of these molecules and spontaneous and artificial metastases implies that tumor cells with low E-cadherin and beta-catenin content have increased ability to enter the vascular circulation at the primary tumor site and to colonize distant tissues.
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PMID:Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas. 1041 Nov 10


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