Abstract 5925: Mapping the molecular communication within the tumor microenvironment of pancreatic cancer as well as between tumor and peritumoral tissue

Abstract

Abstract We are analyzing in detail the molecular communication between the different cell types in the microenvironment of pancreatic ductal adenocarcinomas (PDAC). Also, its regulation is being investigated, looking at aspects such as the kind and mixture of molecules needed for triggering a particular regulative function, and unraveling the inter- and intracellular processes utilized to transmit a molecular message. Although a rare tumor entity, adding up to only about 3% of all cancer cases in the Western world, PDAC is the fourth most frequent cause of cancer-related death; mortality is nearly identical to incidence. There is no real remedy apart from surgery, which can be applied to only 10 to 20% of patients. Even then, basically all patients will experience tumor recurrence. Our study is based on a large basic set of data at the levels of DNA, RNA and protein that was generated from some 1000 pancreatic tumor samples [1], supplemented with information from studies that aim at an elucidation of functional molecules and comparative analyses in other tumors. This has already led to the creation of basic functional knowledge about metastasis [e.g., 2], the establishment of means for diagnosis [3, 4], an accurate disease prognosis [1], the characterization of communication processes [5] and the identification of new therapeutic avenues [6]. At the conference, we will report about the status of mapping particularly the protein-mediated communication between the different cell types in the tumor microenvironment. Also, we will show results about the effect that PDAC tissue has on the wider peritumoral environment and vice versa. The peritumoral tissue is exhibiting a field defect that does not seem to be dependent on DNA-methylation. A comparison of PDAC and cystic pancreatic tumors revealed that differences in communicating with the peritumoral tissue could actually be more important to the known pathological difference between the two cancer entities than the molecular variations in the tumor cells. 1. Bauer et al. (2017), work submitted for publication 2. Botla et al. (2016) Cancer Res. 76, 4149-4159 3. Keller et al. (2014) BMC Med. 12, 224 4. Moskalev et al. (2015) Oncotarget 6, 4418-4427 5. Dror et al. (2016) Nature Cell Biol. 18, 1006-1017 6. Jandaghi et al. (2016) Gastroenterology, in press (doi: 10.1053/j.gastro.2016.08.040) www.dkfz.de/funct_genome/ Note: This abstract was not presented at the meeting. Citation Format: Mohamed S. Alhamdani, Andrea S. Bauer, Jörg D. Hoheisel. Mapping the molecular communication within the tumor microenvironment of pancreatic cancer as well as between tumor and peritumoral tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5925. doi:10.1158/1538-7445.AM2017-5925