- Title
- Proteomic analysis of neuroproteins in pancreatic cancer
- Creator
- Li, Xiang
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2021
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Pancreatic cancer has one of the highest mortality rates among cancers and this is primarily attributed to the absence of early diagnostic biomarkers and no effective targeted therapies. Recent findings have indicated that the infiltration of nerves can generate a positive tumour microenvironment for pancreatic cancer cell growth and dissemination. At the same time, pancreatic cancer cells can drive the outgrowth of nerves in the tumour microenvironment. Fully understanding the molecular mechanisms and mediators involved in this nerve-cancer cells crosstalk, not only provides a better understanding the stimulatory role of nerves in pancreatic cancer progression, but also constitutes a resource for delineating future biomarkers and therapeutic targets. However, detailed understanding of the molecular mechanisms and mediators underpinning the crosstalk between nerves and pancreatic cancer cells remains largely undone. Novel liquid chromatography tandem mass spectrometry (LC-MS/MS) based techniques, shotgun discovery proteomics and parallel reaction monitoring (PRM) targeted proteomics, have provided a wonderful platform to investigate crucial protein events at play in the crosstalk between nerves and pancreatic cancer cells, and to exploit this knowledge for early detection and better intervention in pancreatic cancer. The aims of this thesis were to use LC-MS/MS-based proteomics to discover novel neuroproteins in pancreatic cancer and to understand the role of these proteins in tumour progression and dissemination. More specifically, using shotgun and PRM proteomics analysis, the cellular proteome and secretome of pancreatic cancer cell lines were investigated and compared with that of normal pancreatic ductal epithelial cells. Moreover, we have also analysed the proteome and secretome of Schwann cells, which are the glial cells in peripheral nerves. Several candidate neuroproteins have been identified including cold shock domain containing E1 (CSDE1), galectin-3-binding protein (Gal-3BP), matrix metalloproteinase-2 (MMP-2), cathepsin D (CTSD), plasminogen activator inhibitor-1 (PAI-1), biglycan (BGN), tissue inhibitor of metalloproteinases-2 (TIMP-2), and galectin-1 (Gal-1) and the neurotrophin receptor sortilin. In addition, the function of these proteins in pancreatic cancer was further examined.
- Subject
- pancreatic cancer; human Schwann cells; pathway analysis; PRM proteomic; cold shock domain containing E1; sortilin; thesis by publication; proteome; secretome; neuroproteins; biomarkers; therapeutic targets; LC-MS/MS; shotgun proteomic; label-free quantification
- Identifier
- http://hdl.handle.net/1959.13/1507389
- Identifier
- uon:56016
- Rights
- Copyright 2021 Xiang Li
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 35 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 872 KB | Adobe Acrobat PDF | View Details Download |