Tissue Expression of Sialyl Tn Antigen in Gynecologic Tumors

Numa, Fumitaka; Tsunaga, Nagato; Michioka, Toru; Nawata, Sumihiko; Ogata, Hidenobu; Katô, Hiroshi

doi:10.1111/j.1447-0756.1995.tb01027.x

Cited by 14 publications

(14 citation statements)

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“…in many cancers (25,26), including cervical (27,28), lung adenocarcinomas (29), colorectal carcinomas (30), breast carcinomas (31), and gastric carcinomas (32). Many studies over the past 30 years have shown that the Tn antigen is expressed by >80% of human carcinomas (5-7).…”

Section: Discussionmentioning

confidence: 99%

“…We chose to examine cervical cancer because it has been well documented that Tn and STn antigens are expressed in at least 60% of human cervical carcinomas and their expression is associated with the poor prognosis of the disease (27,28). However, until now, there has been no genetic or biochemical basis for the expression of the Tn/STn antigens in human cancers.…”

Section: Discussionmentioning

confidence: 99%

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Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations inCosmc

Lanneau

Gautam³

et al. 2008

Cancer Research

247

266

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Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression. [Cancer Res 2008;68(6):1636-46]

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations inCosmc

Lanneau

Gautam³

et al. 2008

Cancer Research

247

266

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“…In contrast, normal ovarian epithelia were always found to be STn negative [35,36,37] Some testis cells were occasionally found to be STn positive such as Leydig cells or interstitial cells [1,14,22]. Finally, STn was found at the apical membrane of the ciliated cells of the lung [17,22,38] and at the apical side of the ductal epithelium in normal breast tissue [39,40,41].…”

Section: Stn Immunodetection In Tissues and Tumorsmentioning

confidence: 99%

“…In these different cases, STn over-expression was primarily observed at the apical or luminal cell surface as well as in the corresponding healthy tissues. More unexpectedly, STn was also reported in benign lesions in pancreas [46] and ovaries [35,36,37], two tissues that are devoid of STn expression in the healthy state. Notably, STn staining was observed in pancreatic intraepithelial neoplasia stage III (PanIN3), the last histological grade relevant to benign tumor before the tumor becomes invasive, but not in earlier stages [46,47].…”

Section: Stn Immunodetection In Tissues and Tumorsmentioning

confidence: 99%

Sialyl-Tn in Cancer: (How) Did We Miss the Target?

2012

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Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue α2,6-linked to GalNAcα-O-Ser/Thr. The biosynthesis of STn is mediated by a specific sialyltransferase termed ST6GalNAc I, which competes with O-glycans elongating glycosyltransferases and prevents cancer cells from exhibiting longer O-glycans. While weakly expressed by fetal and normal adult tissues, STn is expressed by more than 80% of human carcinomas and in all cases, STn detection is associated with adverse outcome and decreased overall survival for the patients. Because of its pan-carcinoma expression associated with an adverse outcome, an anti-cancer vaccine, named Theratope, has been designed towards the STn epitope. In spite of the great enthusiasm around this immunotherapy, Theratope failed on Phase III clinical trial. However, in lieu of missing this target, one should consider to revise the Theratope design and the actual facts. In this review, we highlight the many lessons that can be learned from this failure from the immunological standpoint, as well as from the drug design and formulation and patient selection. Moreover, an irrefutable knowledge is arising from novel immunotherapies targeting other carbohydrate antigens and STn carrier proteins, such as MUC1, that will warrantee the future development of more successful anti-STn immunotherapy strategies.

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“…[272][273][274] Im Unterschied dazu wurde in normalen, erwachsenen Geweben keine oder nur wenig Expression beobachtet. In vielen Krebsarten, einschließlich Zervixkrebs, [275,276] Adenokarzinom der Lunge, [277] kolorektales Karzinom, [278] Brustkarzinom [279] und Magenkarzinom, [280] korreliert die Expression des Tn-Antigens mit dem metastatischen Potenzial und einer schlechten Prognose.…”

Section: Krebsunclassified

Das Tn‐Antigen – strukturell einfach und biologisch komplex

Otto

Cummings

2011

Angewandte Chemie

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Die Glycoproteine tierischer Zellen enthalten vielfältige Glycanstrukturen, die co‐ und/oder posttranslational an die Proteine angeheftet werden. Mehr als zwanzig verschiedene Bindungsarten von Glycanen an Proteine sind bekannt, doch sind N‐Glycane (gebunden an Asn) und O‐Glycane (gebunden an Ser/Thr) die häufigsten. Ein abnormes O‐Glycan, das bei Krebs und anderen menschlichen Erkrankungen auftritt, ist das Tn‐Antigen. Es hat eine einfache Struktur, bestehend aus einem N‐Acetyl‐D‐galactosamin, das α‐glycosidisch an einen Serin‐ oder Threoninrest gebunden ist. Das Tn‐Antigen war eines der ersten Glycokonjugate, die chemisch synthetisiert wurden. Es wird normalerweise von einer spezifischen Galactosyltransferase, der T‐Synthase, im Golgi‐Apparat modifiziert. Die Expression aktiver T‐Synthase hängt vom molekularen Chaperon Cosmc ab, dessen Gen auf dem X‐Chromosom liegt. Genmutationen, die die Funktion von T‐Synthase, Cosmc oder anderen an der O‐Glycosylierung beteiligten Faktoren beeinträchtigen, können zur Expression des Tn‐Antigens führen. Da dieses bei einer Reihe von Krankheiten auftritt, besteht großes Interesse, es für die Entwicklung von Impfstoffen und anderen therapeutischen Ansätzen zu nutzen.

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Tissue Expression of Sialyl Tn Antigen in Gynecologic Tumors

Abstract: These findings indicate different behaviors in the appearance of STN in tumor tissue and blood circulation, and also suggest the possible applicability of STN to immunohistochemical diagnosis of squamous-cell carcinomas.

Cited by 14 publications

References 4 publications

Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations inCosmc

Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations inCosmc

Sialyl-Tn in Cancer: (How) Did We Miss the Target?

Das Tn‐Antigen – strukturell einfach und biologisch komplex

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