Within the scope of the action, the researcher introduced mouse models of pancreatic adenocarcinoma to the laboratory and characterized them in regard to the extent and kinetics of perineural invasion. According to previous research, we expected to find instances of perineural invasion in both orthotopic (Jurcak et al. 2019, Gastroenterology) and spontaneous mouse models (Renz et al. 2018, Cancer Cell; Na'ara et al. 2018, Oncogene). Surprisingly, after careful examination of various mouse models we could not detect the typical invasion of cancer cells into nerve trunks as observed in human pancreatic adenocarcinoma patients. Thus, we concluded that mouse models reflect poorly the human perineural invasion. Indeed, recent scientific literature provides data that support our findings (Saricaoglu et al. 2020, Neurogastroenterology & Motility; Jiang et al. 2022, Cancer Letters). Thus, the researcher gained important knowledge about pancreatic adenocarcinoma mouse models, which will be invaluable during the researcher's future research. In addition, this knowledge will be disseminated on the project website. Importantly, the mouse model of pancreatic adenocarcinoma has been used by the researcher to pursue other scientific questions and optimize and introduce protocols for studying pancreas tissue at the transcriptional level.
Within the scope of the action, the researcher obtained FFPE tissue blocks from three human pancreatic adenocarcinoma patients that contained either cancer-invaded nerves or control/uninvaded nerves. The specimens were stained with hematoxylin and eosin, and processed for 10xgenomics CytAssist Visium spatial transcriptomic. The data are of good quality and preliminary analysis on samples coming from one patient identified genes that operate specifically within cancer-invaded nerves. In close future, we will expand the analysis to samples from other patients, confirm major findings using multiplexed immunohistochemistry, and address the functional role of identified factors in driving cancer proliferation or cancer invasiveness with in vitro and in vivo assays. Thus, within the scope of the action, the researcher generated a dataset that will be used to identify gemes operating within cancer-invaded nerves and subsequently experimentally address their functional importance for cancer proliferation and invasiveness. The results will be a basis for the master thesis project of the student and will ultimately be published in the form of scientific publication. Furthermore, the dataset will be used for other scientific projects running in the lab.
