Tumor cells glycoproteins

Tissue-type plasminogen activator (tPA) is a glycoprotein (68 kDa), synthesized by endothelial and tumor-cells. As a serine protease, tPA hydrolyses Arg561-Val562 peptide bond in plasminogen, resulting in plasmin formation. It needs cofactors for efficient plasminogen activation. 

Urokinase-type plasminogen activator (uPA, urokinase) is synthesized by endothelial and tumor cells as a single-chain glycoprotein (scuPA) without catalytic activity. When it is converted to a two-chain protein (tcuPA) by plasmin, an active serine protease center develops, which activates plasminogen. Thus, uPA (55 kDa) results in the amplification of fibrinolysis. 

IFNs are natural glycoproteins produced by the cells of most vertebrates in response to the challenge by foreign agents, such as infectious organisms (viruses, bacteria, fungi, and parasites), and by tumor cells. IFNs can be produced by cells of the innate and adaptive immune systems and by non-immune cells such as fibroblasts and epithelial cells. 

Tumor cells may become resistant when genetic changes occur during cell proliferation. Resistant cancer cells with the mdr-1 gene may possess a membrane-associated protein, p-glycoprotein, that facilitates efflux of chemotherapy agents out of the cells. Numerous attempts at blocking this efflux pump have been unsuccessful. 

ATPase activity of P-glycoprotein related to emergence of drug resistance in Ehrlich ascites tumor cell lines, Biochim. Biophys. Acta 1997,... 

P-glycoprotein is not only expressed in tumor cells, but also in cells of several healthy tissues. In liver it was detected in the biliary canalicular surface of hepato-cytes and the apical surface of small biliary ductules. In the small intestine and colon, it is localized in the apical surface of columnar epithelial cells, and in kidneys it is found in the brush border membrane of proximal tubules. Moreover, it is detectable on the apical surface of small ductules in the pancreas and on the surface of cells in the medulla and cortex of adrenals [2]. 

Recently, Oryza sativa L. japonica cv. Dongjin cell cultures were used to produce an antibody against the tumor-associated glycoprotein 72 (TAG 72). TAG 72 is commonly expressed in human adenocarcinoma cells. Recombinant antibody purified from transgenic rice cells was shown to bind human LS 174T colon adenocarcinoma cells expressing TAG 72. This proved the ability of rice cells to produce a functional foreign protein. 

N-Acetvlneuraminic Acid Aldolase. A new procedure has also been developed for the synthesis of 9-0-acetyl-N-acetylneuraminic acid using the aldolase catalyzed reaction methodology. This compound is an unusual sialic acid found in a number of tumor cells and influenza virus C glycoproteins (4 ). The aldol acceptor, 6-0-acetyl-D-mannosamine was prepared in 70% isolated yield from isopropenyl acetate and N-acetyl-D-mannosamine catalyzed by protease N from Bacillus subtilis (from Amano). The 6-0-acetyl hexose was previously prepared by a complicated chemical procedure (42.) The target molecule was obtained in 90% yield via the condensation of the 6-0-acetyl sugar and pyruvate catalyzed by NANA aldolase (Figure 6). With similar procedures applied to KDO, 2-deoxy-NANA and 2-deoxy-2-fluoro-NANA were prepared from NANA. 

Smyth MJ, Drasovskis E, Sutton VR, Johnstone RW (1998) The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. Proc Natl Acad Sd USA 95 7024-7029... 

Wielinga PR, Heijn M, Broxterman HJ, Lankelma J (1997) P-glycoprotein-independent decrease in drug accumulation by phorbol ester treatment of tumor cells. Biochem Pharmacol 54 791-799... 

Meschini, S., Marra, M., Condello, M., Calcabrini, A., Federici, E., Dupuis, M. L., Cianfriglia, M. and Arancia, G. 2005. Voacamine, an alkaloid extracted from Peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells. International Journal of Oncology, 27(6) 1597-1603. 

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