Abstract 5288: S100PBP is ubiquitously expressed and modulates the function of S100 calcium-binding proteins in pancreatic cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.5288-5288
• Main Authors: Lines, Kate E., Audi, Namaa, Chelala, Claude, Kocher, Hemant, Wijesuriya, Nilu, Hurst, Helen, Crnogorac-Jurcevic, Tatjana
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-5288

We have recently discovered a 37kDa novel S100P-binding protein, S100PBP, which shows no homology to any currently known protein; we have therefore explored its expression in a wide range of normal and cancer tissues, its cellular localization and performed several in vitro functional assays to define its putative roles. In order to determine S100PBP localization in human samples immunohistochemistry was performed on a multi-organ tissue array (Pantomics) and on an in-house made pancreatic ductal adenocarcinoma tissue array including normal, cancer and metastatic lesions. To determine S100PBP function cells with both silenced and stably over-expressing S100PBP were established and investigated by Affymetrix gene expression arrays and a battery of functional assays including adhesion, migration and invasion. We show that this protein is almost ubiquitously expressed, in varying levels, between normal and tumor specimens, which is both cancer- and tissue-type dependent. In normal pancreas it is widely expressed in both exocrine and endocrine compartments while in pancreatic adenocarcinoma its expression is absent in the stroma and retained in some of the cancer cells but with significantly lower intensity. We further show that in addition to S100P, in pancreatic cancer cells S100PBP binds, in a calcium-dependant fashion, several other S100 proteins, namely S100A2, S100A4 and S100A6. Over-expression of S100PBP led to changes in the expression levels of S100P and S100A9, which were down-regulated, and S100A4, which was up-regulated. Furthermore, manipulation of S100PBP expression led to phenotypic changes affecting the adhesive, migratory and invasive capacity of pancreatic cancer cells, that varied depending on the cellular context and constellation of the different S100 proteins present. Both over-expression and silencing of S100PBP also led to an increase/decrease in Cathepsin Z levels, respectively. In summary, S100PBP is ubiquitously expressed and is deregulated in many different cancer types, and appears to play a role in the adhesive, migratory and invasive capabilities of pancreatic cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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):Abstrac