Role of muscarinic signalling in pancreatic cancer

Li, Qian (2022): Role of muscarinic signalling in pancreatic cancer. Dissertation, LMU München: Faculty of Medicine

Abstract

The role of muscarinic acetylcholine receptors during carcinogenesis has been investigated in different cancer types. In this study, we have shown the expression of CHRM1, CHRM3, CHRM4, CHRM5, and the expression of receptor CHRM3 and CHRM4 in different PDAC cell lines. The receptor function was evaluated by calcium flux and cAMP increase. Herein we proved that PDAC cells express functional CHRM3. CHRM3 stimulation can lead to an increase of intra-cellular calcium in two PDAC cell lines with an epithelial phenotype, DanG cells showed to be the most sensitive cell line in this study. In contrast, CHRM4 stimulation did not induce a significant decrease of cAMP in our hands. Furthermore, CHRM3 stimulation did not reveal a significant effect on cell viability. However, in the DanG cell line, we found a distinct subgroup of cells ex-pressing CHRM3. Cell cycle analysis showed a higher percentage of CHRM3 positive cells in the subG1 early apoptosis subgroup, raising the possibility of CHRM3 being useful as a prognostic or monitoring treatment parameter in PDAC. Analysis of the publicly available ATCC database supported this hypothesis.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Pancreatic cancer, Muscarinic receptor, cell viability, Tumor microenvironment
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 30. November 2022
• 1. Referee: Werner, Jens
• Signature of the printed copy: 0700/UMD 21025