ABNORMAL GLYCOPROTEINS AND GLYCOSYLTRANSFERASES IN HUMAN HEPATOMA
ABNORMAL GLYCOPROTEINS AND GLYCOSYLTRANSFERASES IN HUMAN HEPATOMA
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人肝癌中的异常糖蛋白和糖基转移酶
DOI：
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发表时间：
1980
影响因子：
5.2
通讯作者：
R. Schmied
中科院分区：
文献类型：
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作者：
S. Waxman;Chen;R. Schmied
我们已经报道了肝细胞癌患者血清维生素BIZ含量和血清不饱和BIZ结合能力的异常升高（N。Engl. J. Med. 1973. m 1053-1056）。使用来自其中两名患者的血清进行的研究表明，血清BIZ和不饱和B12结合能力的升高是由于存在异常BIZ结合蛋白（Br. J. Haematol. 1974. 27：229-239）。通过使用维生素BIZ-Sepharose的亲和色谱法从这些患者中的两个的血浆和胸膜液中以均质形式分离该肝癌相关BIZ-结合蛋白（肝癌B12 BP）（J.Clin.Invest. 1975. 56：1262-1270）。该肝癌BlzBP属于B12结合糖蛋白的R型组，并且在以下方面与纯化的人乳和唾液R型蛋白基本上无法区分：（a）免疫学性质;（B）氨基酸组成;（c）分子量;和（d）吸收光谱。然而，肝癌BlzBP是不正常的，因为它含有更多的唾液酸和岩藻糖比牛奶和唾液BIZ结合蛋白。唾液酸含量的差异似乎解释了在四种蛋白质中观察到的电泳迁移率的差异。其中一名患者的肿瘤组织含有10倍于同一患者正常肝脏组织的R型蛋白。肝脏中肿瘤的灌注液具有比血清多5倍的Blz结合蛋白，并且与血清肝癌BIzBP相同。此外，来源于人肝细胞瘤的细胞系（SK-H-MA）产生显著量的与肝细胞瘤BIzBP类似的BIZ结合蛋白，而来自正常肝（Chang）和其他瘤形成的细胞系则不产生（Can. Res. 1977. 37：1908-1914）。这些数据表明，一些肝细胞瘤产生增加的高唾液酸化BIZ结合蛋白，其从血浆中缓慢清除并在那里积累为肝细胞瘤BIPBP。SK-H-MA细胞比Chang细胞含有更多的表面和细胞内唾液酸转移酶活性。SK-H-MA细胞也向培养基中释放大量的唾液酸转移酶，而Chang细胞和其他肿瘤细胞则不会（Clin.Chim. Acta. 1979. 98：225-233）。Chang细胞具有更高的表面半乳糖基转移酶活性，并且比SK-H-MA细胞向培养基中的释放量多两倍。这两种来源的半乳糖基转移酶对UDP-半乳糖、无唾液酸-、无半乳糖-Futuin、无唾液酸-粘蛋白和卵清蛋白具有相似的最适pH、Km值，并且被N-乙酰葡糖胺、N-乙酰半乳糖胺和UTP抑制至相同程度。然而，聚丙烯酰胺凝胶电泳揭示了SK-H-MA细胞产生的半乳糖基转移酶的另外的较慢移动带，而Chang细胞则没有（Proc.Am.副运河Res. 1979. u）：285），其类似于在患有各种类型癌症的患者的血清中发现的同工酶GT I1。SK-H-MA细胞也比Chang细胞释放更多的岩藻糖基转移酶和N-乙酰葡糖胺转移酶。这些数据
We have reported extraordinary elevations of serum vitamin BIZ content and serum unsaturated BIZ-binding capacity in patients with hepatocellular carcinoma (N. Engl. J. Med. 1 9 7 3 . m 1053-1056). Studies using sera from two of these patients indicated that the elevations of serum BIZ and unsaturated B12-binding capacity was due to the presence of an abnormal BIZ-binding protein (Br. J. Haematol. 1974. 27: 229-239). This hepatoma-related BIZ-binding protein (hepatoma B12BP) was isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin BIZ-Sepharose (J. Clin. Invest. 1975. 56: 1262-1270). This hepatoma BlzBP belongs to the R-type group of B12-binding glycoproteins and is essentially indistinguishable from the purified human milk and saliva R-type proteins in terms of: (a) immunologic properties; (b) amino acid composition; (c) molecular weight; and (d) absorption spectra. However, hepatoma BlzBP is abnormal in that it contains more sialic acid and less fucose than the milk and saliva BIZ-binding proteins. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patients. A perfusate of the tumor in the liver had 5 times more Blz-binding protein than did the serum and was the same as the serum hepatoma BIzBP. Furthermore, a cell line (SK-H-MA) derived from human hepatoma produces significant amounts of BIZ-binding protein similar to hepatoma BIzBP, whereas cell lines from normal liver (Chang) and other neoplasia did not (Can. Res. 1977. 37: 1908-1914). These data suggest that some hepatomas produce increased hypersialylated BIZ-binding protein that is cleared slowly from the plasma and accumulates there as hepatoma BIPBP. The SK-H-MA cells contain more surface and cellular sialyltransferase activity than Chang cells. The SK-H-MA cells also release large amounts of sialytransferase into the culture medium, whereas Chang cells and other neoplastic cells do not (Clin. Chim. Acta. 1979. 98: 225-233). Chang cells have more surface galactosyltransferase activity and release twice more into the medium than SK-H-MA cells. These two sources of galactosyltransferase have similar pH optima, Km values for UDP-gal, asialo-, agalacto-futuin, asialo-mucin, and ovalbumin, and are inhibited to the same extent by N-acetylglucosamine, N-acetylgalactosamine and UTP. However, polyacrylamide gel electrophoresis revealed an additional slower moving band of galactosyltransferase produced by the SK-H-MA cell, but not by the Chang cell (Proc. Am. Assoc. Can. Res. 1979. u): 285), which is similar to isoenzyme GT I1 found in the serum of patients with various types of cancer. SK-H-MA cells also release more fucosyltransferase and N-acetylglucosaminytransferase than Chang cells. These data