Leung, Edmund (2009) Cyclooxygenase-2 and its role in colorectal cancer metastasis. MD thesis, University of Warwick.

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Abstract

Studies have shown that elevated COX2 expression in colorectal cancer is associated with enhanced metastasis, although the mechanism is unclear. Cancer cells are characterised by the ability of invasive cells detaching from the primary site by downregulation of adhesion molecules such as E-Cadherins. Subsequently, these cells invade through basement membrane onto extracellular matrix by metalloproteinases (MMP). Interaction of cells and extracellular matrix involves cell adhesion molecules such as CD44 and b1-integrins. Finally, intravasation requires cancer cells adhering onto endothelium, an interaction between epithelial Sialyl-Lewis Antigens (SLAs) and endothelial (E)-Selectins. Colorectal cancer cell lines (HT29, CaCO2 and Colo205) and human dermal microvascular endothelial cells (HDMECs) were subjected to different agents (LPS, butyrate, dexamethasone, PGE2 and NS398) in order to determine their COX2, MMP2, E-Cadherins, b1-integrins, CD44, SLAs and E-selectins expression. An index of cells’ invasive potential was assayed using Matrigel chamber simulating extracellular matrix and coculture with HDMECs. HT29 expressed more COX2 than CaCO2. Colo205 was COX2-negative. LPS induced COX2 expression in HT29 but had no significant effects on CaCO2 and Colo205, whereas dexamethasone was inhibitory to the same effect. Butyrate did not demonstrate any significant changes to COX2 expression in all cell lines. NS398 caused a dose and time-dependent inhibition of COX2 activity, as demonstrated by PGE2 assay.

Item Type:	Thesis or Dissertation (MD)
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Library of Congress Subject Headings (LCSH):	Colon (Anatomy) -- Cancer -- Research, Metastasis -- Research, Endothelium -- Diseases
Date:	June 2009
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	MD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Morris, A. G. (Alan George) ; Williams, Nigel
Sponsors:	South Warwickshire Nuffield Surgeons’ Trust (SWNST) ; Murphy, Paul
Format of File:	pdf
Extent:	184 leaves : ill., charts
Language:	eng
URI:	http://wrap.warwick.ac.uk/id/eprint/3160

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