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

Two distinct classes of cell surface FGF-binding proteins have been identified. These receptors differ in both mode of interaction and in affinity for the FGFs. cDNAs that encode the low-affinity receptor were isolated from a hamster kidney cell line cDNA library by expression cloning. Transfected cells that contained these heparan sulfate proteoglycan FGF receptor cDNAs were enriched for by panning on basic FGF-coated plates. The analogous human cDNA was isolated from a hepatoma cell line cDNA library. The homology of our hamster cDNAs to the previously described murine integral membrane proteoglycan syndecan, together with an exact amino acid sequence match of our human-cDNA-encoded product to human syndecan, clearly indicates the identity of these independently isolated proteoglycans. Further confirmation that the expressed molecule serves as a proteoglycan core protein was achieved by immunoprecipitation of 35SO4-labeled material from solubilized transfected cells. Nitrous acid treatment and chondroitinase digestion revealed that 77% of the label was associated with heparan sulfate chains and 22% with chondroitin sulfate chains. These heparan sulfate chains contributed to the fivefold increase in the total heparan sulfate found to be present on the surface of the transfected cells compared with cells transfected with a vector lacking the cDNA insert.
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PMID:The molecular biology of heparan sulfate fibroblast growth factor receptors. 166 83

We have investigated the glycosaminoglycan composition of normal human liver, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma. Uronic acid increased about 4 fold in the benign and reactive lesions, and greater than 7 fold in the carcinoma. Whereas in focal nodular hyperplasia and adenoma dermatan sulfate was the predominant glycosaminoglycan, in hepatocellular carcinoma chondroitin sulfate was the predominant species; it increased 24 fold over normal liver and 3-5 fold over all the other tissues. HPLC analysis of chondroitinase ABC or AC digests showed a 58 fold increase in Delta-Di-OS disaccharides in hepatocellular carcinoma, indicating significant undersulfation of chondroitin sulfate. Surprisingly, the normal-appearing liver surrounding the carcinoma showed glycosaminoglycan changes similar to adenoma and nodular hyperplasia. These results thus indicate that specific glycosaminoglycan changes occur in hepatocellular carcinoma, and suggest for the first time that proteoglycan metabolism is also altered in the non-cirrhotic, hepatic parenchyma adjacent to liver carcinoma.
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PMID:Altered glycosaminoglycan composition in reactive and neoplastic human liver. 215 32

Hepatocellular carcinoma (HCC) possessed the ability of vascular invasiveness toward hepatic portal vein on the process of progression. This biological character of HCC can influence the patients survival on clinically. In this paper, we tried to establish the in vitro portal invasion model with human materials. The hepatic portal vein endothelial cell (HPVEC) derived from intrahepatic portal veins by surgically, have been propagated, as outgrowth cultures in RPMI-1640 medium with 10% fetal bovine serum, on permeable collagen membranes (KOKEN, Tokyo) containing mainly type I collagen, covered with a solubilized tissue basement membrane (MATRIGEL, Collaborate Res., Inc., Bedford MA) involving type IV collagen, laminin and proteoglycan. The primary cultured HPVEC with polygonal shaped cells forming a pavement stone sheet, were positively stained with Factor VIII related antigen and synthesized both prostacyclin and collagenase inhibitor. Co-culture of primary human HPVEC and HuH-7 (human HCC cell line obtained from Prof. Satoh, Okayama Univ.,) cells were inoculated onto reverse side between collagen membrane and gell formed basement membrane. Morphological alterations on the side of HPVEC can be obtained such as polylayered cells and different cytoplasmic cells among HPVEC. These results indicate that this experimental model can provide an useful in vitro model for the study of HCC portal invasion.
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PMID:[An attempt of in vitro portal invasion model of hepatocellular carcinoma utilizing permeable collagen membrane]. 256 88

The use of a hyaluronic acid-binding proteoglycan (hyaluronectin) as a probe for the detection of hyaluronic acid has facilitated the development of an indirect enzymo-immunological assay for hyaluronidase. Plastic microtest ELISA plates were coated with hyaluronic acid. Incubation with hyaluronidase led to the destruction of insolubilized hyaluronic acid in proportion to the hyaluronidase concentration of samples. Residual hyaluronic acid was assayed by its capacity to bind immune complexes made up of hyaluronectin supplemented with alkaline phosphatase-conjugated anti-hyaluronectin antibodies. The technique was very sensitive and permitted the detection of as little as 10(-10) NFU of bovine testicular hyaluronidase. Hyaluronidase was detected by this technique in human sera, bee venom and culture medium of human hepatoma cell lines.
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PMID:An indirect enzymoimmunological assay for hyaluronidase. 331 96

From the culture medium of Lentinus edodes mycelia, water-soluble material (LEM) was prepared and further fractionated by alcohol precipitation and gel filtration on Sepharose 6B. The resulting fraction of xylose-rich proteoglycan at the void volume was designated as LAP1. The 25% and 50% survival rates of hepatoma-bearing rats were raised by intraperitoneal (i.p.) administration of LAP1 at doses of 3-10 mg/kg (an optimum dose, 3 mg/kg). This fraction did not suppress in vitro cell proliferation of the hepatoma. Moreover, the i.p. administration of LAP1 significantly augmented the activity of macrophage-migration inhibition of the splenic cells from hepatoma-bearing rats in the early stage after transplantation. Thus, the anticarcinogenic action of LAP1 would partly be interpreted by host-dependent immunomodulation.
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PMID:Anticarcinogenic action of an alcohol-insoluble fraction (LAP1) from culture medium of Lentinus edodes mycelia. 403 72

A rat hepatoma cell line was shown to synthesize heparan sulfate and chondroitin sulfate proteoglycans. Unlike cultured hepatocytes, the hepatoma cells did not deposit these proteoglycans into an extracellular matrix, and most of the newly synthesized heparan sulfate proteoglycans were secreted into the culture medium. Heparan sulfate proteoglycans were also found associated with the cell surface. These proteoglycans could be solubilized by mild trypsin or detergent treatment of the cells but could not be displaced from the cells by incubation with heparin. The detergent-solubilized heparan sulfate proteoglycan had a hydrophobic segment that enabled it to bind to octyl-Sepharose. This segment could conceivably anchor the molecule in the lipid interior of the plasma membrane. The size of the hepatoma heparan sulfate proteoglycans was similar to that of proteoglycans isolated from rat liver microsomes or from primary cultures of rat hepatocytes. Ion-exchange chromatography on DEAE-Sephacel indicated that the hepatoma heparan sulfate proteoglycans had a lower average charge density than the rat liver heparan sulfate proteoglycans. The lower charge density of the hepatoma heparan sulfate can be largely attributed to a reduced number of N-sulfated glucosamine units in the polysaccharide chain compared with that of rat liver heparan sulfate. Hepatoma heparan sulfate proteoglycans purified from the culture medium had a considerably lower affinity for fibronectin-Sepharose compared with that of rat liver heparan sulfate proteoglycans. Furthermore, the hepatoma proteoglycan did not bind to the neoplastic cells, whereas heparan sulfate from normal rat liver bound to the hepatoma cells in a time-dependent reaction. The possible consequences of the reduced sulfation of the heparan sulfate proteoglycan produced by the hepatoma cells are discussed in terms of the postulated roles of heparan sulfate in the regulation of cell growth and extracellular matrix formation.
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PMID:Structure and properties of an under-sulfated heparan sulfate proteoglycan synthesized by a rat hepatoma cell line. 623 Mar 67

Proteoglycan (heparan sulfate-protein conjugate) was solubilized with 8 M urea from rat liver plasma membranes after enzymic (RNAase, neuraminidase) treatments and extensively purified by chromatography and gel filtration. The final products gave an average ratio of hexuronate to protein (weight) of approx. 1.5, contained hexosamine equimolar to hexuronate and were sensitive to beta-elimination (the molecular weight being reduced from 20 . 10(4) to 3 . 10(4) (gel filtration)). The proteoglycan fraction, when added to trypsinized and untrypsinized ascites hepatoma (AH-130F(N)) cells, inhibited the concanavalin A-mediated agglutination of the cells. However, the alkali-treated proteoglycan (beta-elimination) or acid mucopolysaccharide fraction prepared from liver plasma membranes by papain digestion were less effective, and a reference preparation of heparan sulfate was almost ineffective. It was confirmed that significant amounts of proteoglycan labelled with 35SO4(2-) were firmly bound to or taken up by the trypsinized ascites hepatoma cells. These results together with the sensitization of lectin-mediated agglutination by mild protease treatment of cells suggest that cell surface proteoglycans may act as a negative modulator in the lectin-mediated agglutination of cells.
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PMID:Cell surface proteoglycans as a negative modulator in concanavalin A-mediated agglutination of hepatoma cells. 739 52

We have isolated a population of post-TGN secretory vesicles from hepatocytes. These vesicles of 100-150 nm diameter carry heparan sulfate proteoglycans. Secretory proteins (albumin, apo-lipoprotein E, fibrinogen) are sorted into different post-TGN secretory vesicles. A member of the ARF family of small GTP-binding proteins is associated with these vesicles. A unique peripheral membrane protein of these vesicles (VAPP14) was shown to exist also on the TGN. Brefeldin A leads to a dissociation of VAPP14 from the TGN. Antibodies against VAPP14 inhibit budding of proteoglycan containing vesicles from the TGN in a cell-free system. Inhibition occurred also in the presence of GTP-gamma-S. The same type of vesicles exists in H35 Reuber hepatoma cells.
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PMID:Sorting and budding of constitutive secretory vesicles in hepatocytes and hepatoma cells. 757 49

Addition of apolipoprotein (apo) E to rabbit beta-very low density lipoproteins (beta-VLDL) has been shown to result in a marked enhancement of their binding and uptake by various cell types. Apolipoprotein E binds to lipoprotein receptors and proteoglycans. To distinguish between apoE binding to these sites, cells were treated with heparinase. Heparinase treatment of receptor-negative familial hypercholesterolemic (FH) fibroblasts and human hepatoma cells (HepG2) released 30-40% of newly synthesized cell surface 35S-labeled proteoglycans and decreased the binding of beta-VLDL+apoE to FH and normal fibroblasts and HepG2 cells by more than 80%. Furthermore, heparinase treatment significantly decreased the uptake of fluorescently labeled beta-VLDL+apoE by HepG2 cells and decreased cholesteryl ester synthesis in FH fibroblasts by 75%. Likewise, canine chylomicron remnants enriched in apoE demonstrated enhanced binding that was 80% inhibited by heparinase treatment of HepG2 cells. Heparinase treatment did not affect beta-VLDL (without added apoE) or low density lipoprotein (LDL) binding to these cells or the binding activity of beta-VLDL+apoE to the LDL receptor-related protein (LRP) or to the LDL receptor on ligand blots. Chinese hamster ovary (CHO) mutant cells lacking the synthesis of either heparan sulfate (pgsD-677) or all proteoglycans (pgsA-745) did not display any enhanced binding of the beta-VLDL+apoE. By comparison, wild-type CHO cells demonstrated enhanced binding of beta-VLDL+apoE that could be abolished by treatment with heparinase. These mutant cells and wild-type CHO cells possessed a similar amount of LRP, as determined by ligand blot analyses and by alpha 2-macroglobulin binding, and possessed a similar amount of LDL receptor activity, as determined by LDL binding. Therefore, we would interpret these data as showing that heparan sulfate proteoglycan may be involved in the initial binding of the apoE-enriched remnants with the subsequent involvement of the LRP in the uptake of these lipoproteins. It remains to be determined whether the heparan sulfate proteoglycan can function by itself in both the binding and internalization of the apoE-enriched remnants or whether the proteoglycan is part of a complex with LRP that mediates a two-step process, i.e. binding and subsequent internalization by the receptor.
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PMID:Role of heparan sulfate proteoglycans in the binding and uptake of apolipoprotein E-enriched remnant lipoproteins by cultured cells. 768 68

The biological activity of many cytokines is regulated by binding proteins present at the cell surface, in extracellular matrices or in soluble phase. We describe here a TGF-beta binding protein that is both an extracellular matrix and a cell surface protein. When intact extracellular matrices of HEP-G2 cells were affinity cross-linked with 125I-TGF-beta 1, two major binding components were seen: a 250-kD, proteoglycan-like molecule, presumed to be betaglycan, and a 60-kD protein. The 60-kD TGF-beta-binding protein was also present at the cell surface. It could be released from the cell surface by treating cells with high salt, heparin, chondroitin sulfate, heparitinase, or chondroitinase, indicating that it is bound to heparan sulfate and chondroitin sulfate proteoglycans. The 60-kD protein bound TGF-beta 1 with an apparent dissociation constant of 1.6 nM, and there were 30,000 binding sites per cell at the cell surface. In addition to the HEP-G2 cells and another hepatoma cell line, the 60-kD protein was also found in a human colon carcinoma (HT-29) cell line but not in rat kidney (NRK-49F) or human fibroblast (HUT-12) cell lines. The 60-kD protein could be extracted from cells containing it and transferred to the surface of previously negative cells. The 60-kD protein may serve to regulate the binding of TGF-beta to its signal transducing receptors by targeting TGF-beta to appropriate locations in the microenvironment of cells.
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PMID:A 60-kD protein mediates the binding of transforming growth factor-beta to cell surface and extracellular matrix proteoglycans. 833 95


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