Buted its own repertoire of glycoproteins. Altogether only 14 proteins were identified > 자유게시판

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Buted its own repertoire of glycoproteins. Altogether only 14 proteins were identified in all 12 cell lines and a new subset of glycoproteins was found [52]. These findings suggest distinct O-glycoproteomes for each type of cancer, however, further investigations are needed to gain insights into its possible therapeutic value. Targeting of tumor specific O-glycoslyation is a promising treatment strategy for cancer, but faces various challenges. After Tn antigen administration, a sufficient immune and anti-tumor response in nonhuman primates was induced [53]. Thereafter, Tn antigen evolved to an important component of glycoconjugate based anti-tumor vaccines [5, 54]. Springer and colleagues reported a successful vaccination of 16 breast cancer patients with a statistical significant better survival, however, the validity of their data cannot be determined due to the absence of several controls as well as appliance of a questionable glycoprotein preparation [55]. The treatment of prostate cancer was another focus of Tn antigen based vaccination. In a phase I clinical trial, all patients developed an immune response against Tn antigen, but only 33 achieved favorable clinical responses with decreased detection of prostate-specific antigen [56]. Long-term survival data have not been published so far, but these studies might provide a first prospect whether Tn antigen vaccination results in favorable effects in patients. Nonetheless, to provide a substantiate basis for successful vaccination with Tn antigen, a proper antigen expression is required. Since the first discovery of Tn antigen, a variety of methods have been developed, mostly being dependent on either antibodies or lectins. A high number of different GalNAc-binding lectins or antibodies are PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/10956013 available and were already successfully applied in various expression studies of human cancers, including pancreatic cancer. Unfortunately, the results of these studies showed no consistency, which might be a consequence of different binding specificities of individually used lectins and antibodies. Tn antigen binding lectins and antibodies may also cross-react with other carbohydrate antigens [51]. In addition, monoclonal antibodies recognize not only the Tn antigen but also depend on the individual amino acid backbone of the protein, leading to a distinct recognition pattern of Tn containing glycoproteins on cancer cells [50]. Altogether, pancreatic cancer has most likely its specific glycoproteome and hence the need arises for its specific detection. Here, we focused on the identification of aberrant O-glycosylated proteins in pancreatic cancer. The proteins identified may contribute to a better understanding of the pancreatic cancer O-glycoproteome and may help to develop pancreatic cancer specificvaccinations or other therapies in future. Therefore, membrane-associated proteins were of pivotal interest, because they represent potential targets for immunotherapy. We evaluated all 23 O-glycoproteins regarding their localization in cancer, involvement in signal transduction and focused our analysis on four proteins for further characterization (Tab. 1). In this study, Tn antigen expression was confirmed for Nucleolin, Capecitabine GRP-78, Enolase and Annexin A2 using a VVL-based immunoprecipitation and all other identified Tn antigen carrier proteins were predicted to be highly O-glycosylated by the ISOGlyP database. Moreover, we could clearly show that Nucleolin is frequently co-localized with Tn antige.