Abstract 3311: Glycosylation alterations associated with pancreatic cancer EMT probed using gene expression in three model systems
| Autor: | Vincent M. Paulino, Venkat Keshamouni, Juli Ross, Jeremy A. Miller, Craig P. Webb, Nhan L. Tran, Kevin A. Maupin, Brian B. Haab, Arkadeep Sinha, Michael E. Berens |
|---|---|
| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:3311-3311 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am10-3311 |
| Popis: | The lethal nature of pancreatic cancer is related to its propensity to disseminate at early stages and its resistance to chemotherapeutics. Cancer cells that have undergone epithelial-mesenchymal transition acquire these traits and may play an important role in pancreatic cancer progression. The identification of the defining molecular features and functional drivers of pancreatic cancer EMT may lead to new methods to control cancer progression. Particular glycosylation patterns are specifically associated with cellular differentiation and activation and play functional roles in cell migration and signal transduction. Therefore we hypothesized that pancreatic cancer EMT is characterized by specific glycosylation alterations that play functional roles in cancer cell differentiation or migration. As a first step toward investigating that hypothesis, we characterized the expression of glycan-related genes in three model systems of pancreatic cancer EMT. We used whole-genome microarrays to study gene expression in: 1) TGF-beta-induced EMT in two different cell lines; 2) a panel of 23 pancreatic cancer cell lines characterized as either epithelial-like or mesenchymal-like; and 3) actively-migrating and stationary cells from two different cell lines. We compiled a list of 585 genes involved in glycosylation (biosynthesis, sugar transport, glycan-binding, etc.) or EMT. Using this list, we found that each model system displayed both elevations and reductions with high significance in multiple glycan-related genes. The percentage of glycan-related genes showing changes exceeded the percentage of overall genes showing changes in each case, suggesting an important role of glycan alterations in EMT. To narrow the list of candidate genes for further study, we looked at the overlap in altered genes between the model systems. ST6GALNAC4, an enzyme that transfers sialic acid to particular presentations of the N-acetyl galactosamine monosaccharide, was elevated in the pancreatic cancer cell lines of all model systems. Glycan structures similar to those synthesized by ST6GALNAC4 are commonly associated with cancer. Genes involved in the sulfation and de-sulfation of glycosaminoglycans were frequently altered, as well as members of the mannose receptor family, each of which suggests routes of modulating extracellular interactions. These results support the involvement of glycan alterations in cancer EMT and suggest targets for the further study of mechanistic drivers of pancreatic cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3311. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|