Search the site

The University of Manchester Library

In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

New Insights into the Cellular Lipid Cascade Using Infrared Microspectroscopy

Gladwell, Thomas Alexander

[Thesis]. Manchester, UK: The University of Manchester; 2019.

Access to files

Abstract

Although prostate cancer is the most diagnosed cancer in men worldwide, there is geographical variance in both incidence and morbidity, with higher trends in Westernised developed countries. In particular, the high levels of the omega-6 polyunsaturated fatty acid arachidonic acid (AA) in Western diets has been shown to promote aggressive prostate cancer in vitro. However, the exact mechanism through which AA induces the aggressive phenotype has not been fully characterised. Here Fourier transform infrared microspectroscopy (FT–IRM) coupled with fluorescence microscopy (FM) was used to follow AA metabolism in prostate cancer cell lines. Using partially deuterated AA, (d8-AA), with a distinctive C-D stretch seen at 2251 cm–1 providing molecular specificity, coupled with Nile Red Fluorescence imaging, it has been shown that, unlike the non-invasive prostate cancer cell lines PNT2 and LNCaP, invasive prostate cancer lines PC-3M, PC-3. LNCaP C4-2B and DU145 readily uptake and metabolise AA, producing prostaglandin E2 (PGE2) via the cyclooxygenase-2 (COX-2) pathway. Inhibition of the COX-2 pathway with NS938 reduces the invasive stimulus of AA and blocks the uptake of AA. Similarly, the addition of the omega-3 poly unsaturated fatty acid Docosahexaenoic acid (DHA), previously shown to inhibit AA induced invasion, inhibited cellular AA uptake in invasive cell line PC-3. In conclusion, it has been demonstrated that FT–IRM can be utilised to follow metabolomics processes within a prostate model and provide an insight to the molecular pathways underlying the metabolome. This could play a pivotal role in understanding the chemistry and behaviour of the initiation of metastatic prostate cancer.

Additional content not available electronically

Non

Non

Bibliographic metadata

Type of resource:
Content type:
Administered thesis
Form of thesis:
Traditional
Type of submission:
Doctoral level ETD - final
Thesis title:
New Insights into the Cellular Lipid Cascade Using Infrared Microspectroscopy
Degree type:
Doctor of Philosophy
Degree programme:
PhD Chemical Engineering & Analytical Science
Publication date:
2019-02-26T21:31:11
Institution:
The University of Manchester
Location:
Manchester, UK
Total pages:
229
Abstract:
Although prostate cancer is the most diagnosed cancer in men worldwide, there is geographical variance in both incidence and morbidity, with higher trends in Westernised developed countries. In particular, the high levels of the omega-6 polyunsaturated fatty acid arachidonic acid (AA) in Western diets has been shown to promote aggressive prostate cancer in vitro. However, the exact mechanism through which AA induces the aggressive phenotype has not been fully characterised. Here Fourier transform infrared microspectroscopy (FT–IRM) coupled with fluorescence microscopy (FM) was used to follow AA metabolism in prostate cancer cell lines. Using partially deuterated AA, (d8-AA), with a distinctive C-D stretch seen at 2251 cm–1 providing molecular specificity, coupled with Nile Red Fluorescence imaging, it has been shown that, unlike the non-invasive prostate cancer cell lines PNT2 and LNCaP, invasive prostate cancer lines PC-3M, PC-3. LNCaP C4-2B and DU145 readily uptake and metabolise AA, producing prostaglandin E2 (PGE2) via the cyclooxygenase-2 (COX-2) pathway. Inhibition of the COX-2 pathway with NS938 reduces the invasive stimulus of AA and blocks the uptake of AA. Similarly, the addition of the omega-3 poly unsaturated fatty acid Docosahexaenoic acid (DHA), previously shown to inhibit AA induced invasion, inhibited cellular AA uptake in invasive cell line PC-3. In conclusion, it has been demonstrated that FT–IRM can be utilised to follow metabolomics processes within a prostate model and provide an insight to the molecular pathways underlying the metabolome. This could play a pivotal role in understanding the chemistry and behaviour of the initiation of metastatic prostate cancer.
Additional digital content not deposited electronically:
Non
Non-digital content not deposited electronically:
Non
Keyword(s):
Thesis main supervisor(s):
Thesis co-supervisor(s):
Funder(s):
Degree grantor:
Language:
en

Institutional metadata

University researcher(s):
Academic department(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:318550
Created by:
Gladwell, Thomas
Created:
26th February, 2019, 21:31:11
Last modified by:
Gladwell, Thomas
Last modified:
6th March, 2019, 11:31:40

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.