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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha-GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl-oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H-labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl-alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19-9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells.
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PMID:Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer-associated antigens in human colon cancer cells. 128 81

A monoclonal antibody, Onc-M26, that recognizes a cancer-associated antigen expressed by most human adenocarcinomas of the breast was shown previously to recognize a carbohydrate epitope carried on a hexaglycosyl ganglioside carrying the sialyl-Lewis X (SLex) antigen (P.S. Linsley et al., 1988, Cancer Res. 48, 2138-2148). Evidence that the antibody binds even more avidly to minor gangliosides containing more complex carbohydrate chains prompted us to search for a higher affinity epitope among sialylated oligosaccharides from pooled human milk. Affinity chromatography of a partially purified fraction of monosialylated milk oligosaccharides on a column containing monoclonal antibody Onc-M26 bound to a macroporous silica matrix gave a peak with a retention volume significantly greater than that of a standard SLex-active hexasaccharide. The retained material consisted of two nonasaccharides, each containing the SLex tetrasaccharide sequence, Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3) GlcNAc, linked beta 1-6 to a 3,6-disubstituted galactosyl residue.
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PMID:Isolation of two novel sialyl-Lewis X-active oligosaccharides by high-performance liquid affinity chromatography using monoclonal antibody Onc-M26. 134 41

Sialyl Lex-i (SLX) concentrations in the extracts of noncancerous and cancerous tissues of various human organs were determined by radioimmunoassay for detailed evaluation of SLX. Cancerous tissues had significantly elevated SLX concentrations compared with noncancerous tissues of various organs. Tissue SLX concentration of the cancerous part was significantly higher than that of the adjacent noncancerous part in the same tissue. There was no significant correlation between tissue SLX concentration and serum SLX level. Positive localization of SLX was clearly observed in such cancerous tissues by immunohistochemical study, although not in any noncancerous tissues. Each of the antigens: SLX, CA 19-9, carcinoembryonic antigen, and CA 125 showed a different distribution pattern in tissue concentration or localization in various organs. These results indicate that SLX may be a valuable cancer-associated antigen produced by malignant tissues, suggesting its clinical application as a tumor marker.
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PMID:Elevated tissue concentrations of sialyl Lex-i in cancerous tissues compared with those in noncancerous tissues of various organs. 204 31

Several major alterations in glycosylation of glycoproteins and glycolipids occur in colorectal cancer resulting in the expression of cancer associated antigenic epitopes. These changes can occur either in the outer peripheral, middle, or inner core regions of the carbohydrate side chains. The major changes are increased expression, inappropriate expression, deletion and modification of antigenic structures present in normal colorectal tissues. These changes are illustrated by recent studies on the expression of several blood group antigens such as A,B,H, and Leb antigens, modified blood group related antigens such as sialosyl Lea, CA 50, SPan-1, Lex (X) and Ley (Y) antigens and inner core carbohydrate antigen such as T, Tn and Sialosyl-Tn antigens. These changes also occur in adenomatous polyps and appear to correlate with parameters of malignant potential. Thus, these carbohydrate antigens may serve as premalignant markers which may be useful in identification and screening of subjects at high risk for developing colorectal cancer. Carbohydrate containing cancer and malignant markers show considerable promise as potential candidates in immunodetection, staging and therapy of colorectal cancer.
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PMID:Carbohydrate antigen expression in colorectal cancer. 210 94

Cell surface carbohydrates are excellent markers of cellular differentiation and maturation processes due to their great structural and antigenic diversity as well as their known biosynthetic precursor/product relationships. Using a panel of monoclonal antibodies with well-defined carbohydrate specificities we have studied the expression of biosynthetically related antigens in normal and psoriatic skin. Two "families" of carbohydrate structures were investigated. One series of structures based on N-acetyllactosamine chains (type 2 chain: N-acetyllactosamine and fucosylated derivates hereof of H, Lex, Ley and sialyl-Lex) and another based on the simple mucin type core structures (type 3 chain: Tn, T and sialylated derivates hereof as well as the fucosylated derivative, H). Previously we have found these carbohydrate structures define distinct cell layers in stratified squamous epithelia of mucosa of the cheek, esophagus and uterine cervix. In normal and uninvolved epidermis, N-acetyllactosamine and T carbohydrates were found in the spinous cell layer, whereas the fucosylated derivates, H structures, were found in the granular cell layers above. The fucosylated and sialylated derivate of N-acetyllactosamine, sialylated Lex, had the same distribution as N-acetyllactosamine and T structures. This sequential expression of carbohydrates is similar to our previous findings in mucosa. However, in contrast to mucosa, normal skin basal cells did not label. The glycosylation pattern in psoriatic epithelium was changed in two ways. 1) Some carbohydrates (types 2 and 3 chain H and T) were expressed at an earlier stage of cell maturation. 2) The biosynthetic precursors to T structures, Tn and sialyl-Tn, which are not expressed in normal skin, and are often considered cancer-associated antigens, appeared in psoriatic skin. The Tn-antigen was expressed on basal and lower spinous cells, whereas the sialyl-Tn was only found on basal cells above the dermal papillae. The findings in the present work support previous studies of changes in cell surface glycosylation in psoriatic epidermis and demonstrate the appearance of tumor-associated antigens in highly proliferative, but benign, stratified epithelium.
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PMID:Cell surface glycosylation patterns in psoriasis. 218 Apr 41

In order to explore the relationship between the expression of cancer-associated glycolipids such as sialylated Lex (SLEX) and sialylated Lea (SLEA) and the histological subtypes of lung cancers, 30 cases of small cell carcinoma (SCC) and 47 cases of non-small cell carcinoma (non-SCC) were examined immunohistochemically using monoclonal antibodies reacting with SLEX and SLEA. The forty-seven cases of non-SCC included 20 cases of adenocarcinoma, 20 of squamous cell carcinoma and 7 of large cell carcinoma. Tumour cells of most non-SCCs expressed SLEX and SLEA. In adenocarcinomas, the number of tumour cells having SLEX and SLEA was more than that of squamous cell carcinomas, large cell carcinomas and SCC. In SCC, 14 of the 30 cases were found to be positive for both antigens. Although the cancer cells of 11 cases of 17 intermediate cell type SCC had both antigens, the cells of only 3 of 13 oat cell tumours expressed SLEX and SLEA. The present study shows that SLEX and SLEA are useful markers for lung adenocarcinomas, that most cases of intermediate cell type of SCCs have characteristics similar to non-SCC but that many oat cell tumours lack them.
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PMID:Immunohistochemical examination of lung cancers using monoclonal antibodies reacting with sialosylated Lewisx and sialosylated Lewisa. 302 84

Carbohydrate antigens are useful markers for the serological detection of pancreatic cancer. However, data concerning the expression of structurally well-defined carbohydrate antigens in normal and malignant pancreatic tissue is quite limited. The Lex and Leg antigens are closely related carbohydrate antigens synthesized on type 2 blood group oligosaccharide side chains of glycolipids and glycoproteins. Monoclonal antibodies anti-SSEA-1 and AH6 recognize "simple" Lex and Ley epitopes, respectively, regardless of the length of the carrier carbohydrate. Other monoclonal antibodies recognize Lex (FH4), sialyl Lex (FH6, IB9) or Ley (KH1, CC-1, CC-2) carried only by elongated type 2 side chains with or without internal alpha 1,3 fucosyl substitution. The present comparative immunohistochemical study used tissues of normal pancreas, chronic pancreatitis, and pancreatic cancer to determine the normal expression of Lex and Ley antigens in the pancreas and to elucidate any cancer-associated alterations. Lex-related antigens were not expressed in normal pancreas, expressed in only 10-20% of chronic pancreatitis tissues, but expressed in 50-70% of pancreatic cancer tissues. The frequency of Lex-related antigen expression in pancreatic cancer tissues was lowest in poorly differentiated cancers. Within a given specimen, at least three or all four of the Lex recognizing monoclonal antibodies were simultaneously expressed. Unlike Lex antigens, Ley-related antigens were expressed in 32-77% of specimens of normal pancreas, with similar frequencies in specimens of chronic pancreatitis and pancreatic cancer. In normal pancreas, simple Ley was expressed by both ductal and acinar cells, but extended Ley antigens were expressed only by acinar cells. In pancreatic cancer, extended Ley antigen expression was found in less than 10% of poorly differentiated tumors. Coexpression among the Ley-related antigens was less common than with the Lex-related antigens. Also in cancer specimens, simple Lex and simple Lex antigens were often concordantly expressed, whereas extended Lex and extended Ley antigen expression was often discordant. Hyperplastic ducts and ductules associated with pancreatic cancer expressed Lex-related antigens more frequently than morphologically similar lesions associated with chronic pancreatitis. These results demonstrate that Lex-related antigens are cancer-associated determinants in the human pancreas. The discrepant expression between Lex and Ley antigens in these tissues implies altered regulation of fucosyltransferase activity associated with the malignant state.
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PMID:Lex and Ley antigen expression in human pancreatic cancer. 333 15

Sialyl Lea and sialyl Lex are cancer-associated carbohydrate antigens. The biosynthesis of these antigens is completed by fucosyltransferases. We measured the activity of alpha 1-->4 fucosyltransferase (sialyl Lea synthase) and alpha 1-->3 fucosyltransferase (sialyl Lex synthase) in gastrointestinal cancer tissues. alpha 1-->4 fucosyltransferase activity was similarly detected in most normal or malignant tissues. alpha 1-->3 fucosyltransferase activity in gastric cancer was higher than in the normal mucosa. In colonic cancer, although the enhanced expression of sialyl Lex was observed in 86% of cases, the elevated activity of alpha 1-->3 fucosyltransferase was observed in only 58%. In conclusion, the expression of sialyl Lea and sialyl Lex antigens in the stomach and colon was not controlled solely by fucosyltransferases.
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PMID:[Fucosyltransferase producing sialyl Le(a) and sialyl Le(x) carbohydrate antigen in gastrointestinal cancer]. 763 19

A comparative immunohistochemical study was performed to analyse the expression of cancer-associated carbohydrate antigens by primary and metastatic lesions of colon cancer. We used monoclonal antibodies which reacted with Lea, Lex and Tn as well as their sialylated derivatives. Twenty-one primary lesions in patients without metastasis and 26 primary and metastatic lesions in patients with liver metastasis were studied. Sialyl Lea was expressed by 57% of the primary lesions of patients without metastasis, 65% of the primary lesions of patients with metastasis and 73% of their liver metastases. Sialyl Lex was expressed by 60% of the primary lesions of patients with and without metastasis as well as by approximately 80% of the liver metastases. Sialyl Lea and sialyl Lex showed strong expressions in the liver metastases, significantly greater than in the primary lesions. The findings indicate the increased expressions of sialyl Lea and sialyl Lex to be correlated with liver metastasis of colorectal cancer.
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PMID:Carbohydrate antigens and liver metastasis in colorectal cancer. 790 24

An important outcome of the monoclonal antibody approach for cancer-associated antigens is that cell-surface carbohydrates have been shown to be very important cancer-associated antigens. These antigens are currently classified into several groups. The first group has the sugar determinant carried by so-called type 1 chain carbohydrates, with a backbone structure composed of the Gal beta 1-->3GlcNAc beta repeating unit. The antigens in this group are utilized mainly for the diagnosis of cancers in the pancreas, biliary tract and other digestive organs. This group includes the well-known serum tumor marker, the 2 -->3 sialyl Le(a) antigen, which is detected by N19-9 and other antibodies. This group also includes DU-PAN-2, which was recently confirmed to be the sialyl Lec. The second group has the polysaccharide determinant carried by so-called type 2 chain carbohydrates, the characteristic feature of which is a backbone structure composed of the Gal beta1 -->4GlcNAc beta repeating unit. This group includes the tumor markers, sialyl SSEA-1, CSLEX-1 or sialyl Lewis X, and is used for the diagnosis of cancers originating in the lung, ovary and digestive organs. The third group has the antigenic determinant carried by the innermost core structures in O-linked carbohydrate side chains. The example of this group is the sialyl Tn antigen, which is detected in ovarian cancers. This group also includes the recently described carbohydrate determinant called Fl alpha antigen, which is frequently expressed in gastric cancer cells. Some of the antigens in the first and second groups such as sialyl Le(a) and sialyl Le(x), serve as ligands for E-selectin, a cell adhesion molecule expressed on activated human endothelial cells, and play significant roles in hematogenous metastasis of cancer.
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PMID:[Biological function of cancer-associated carbohydrate antigens]. 869 8


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