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Title: Innate immune surveillance in ovarian and pancreatic cancer
Author: Kaur, Anuvinder
ISNI:       0000 0004 7658 2641
Awarding Body: Brunel University London
Current Institution: Brunel University
Date of Award: 2017
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Activation of innate immune surveillance mechanisms during the development of cancer is well-documented. However, knowledge of how these innate immune proteins, when added exogenously, independent of tumour microenvironment, affect tumour cells is limited. In Chapter 3, the effects of human C1q and its individual globular domains (ghA, ghB and ghC) on an ovarian cancer cell line, SKOV3, have been examined. C1q and globular head modules induced apoptosis in approximately 55% of cells, which involved upregulation of TNF-α and Fas and activation of the caspase cascade. This occurred in parallel to the downregulation of mTOR, RICTOR and RAPTOR survival pathways, which are often over-expressed in the majority of the cancers. Thus, this study provided evidence for another complement-independent role of C1q. The second part of this thesis was to investigate the effect of Human Surfactant Protein-D (SP-D), which is known to modulate secretion of a range of cytokines and chemokines by effector immune cells, such as TNF-a and TGF-β, at mucosal surfaces during infection and inflammation. Our hypothesis was that SP-D can influence these soluble factors as a part of its putative role in the immune surveillance against pancreatic cancer, where the inflammatory tumour microenvironment contributes to the epithelial-to-mesenchymal transition (EMT) invasion and metastases. In this study, a recombinant fragment of human SP-D (rfhSP-D) inhibited TGF-β expression in a range of pancreatic cancer cell lines, thereby reducing their invasive potential by downregulating Smad2/3 expression that may have interrupted signal transduction negatively, which affected the transcription of key mesenchymal genes such as Vimentin, Zeb1 and Snail. Furthermore, prolonged treatment with rfhSP-D induced apoptosis in the pancreatic cancer cell lines via activation of the caspase cascade. Thus, this study added another layer to the well-known protective role of SP-D.
Supervisor: Kishore, U. ; Pathan, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Human surfactant protein D ; C1q ; Globular heads ; Apoptosis