Cyclooxygenase-2 and its role in colorectal cancer metastasis
Leung, Edmund (2009) Cyclooxygenase-2 and its role in colorectal cancer metastasis. MD thesis, University of Warwick.Full text not available from this repository.
Official URL: http://webcat.warwick.ac.uk/record=b2334455~S15
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
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|
|Official Date:||June 2009|
|Institution:||University of Warwick|
|Theses Department:||Department of Biological Sciences|
|Supervisor(s)/Advisor:||Morris, A. G. (Alan George) ; Williams, Nigel|
|Sponsors:||South Warwickshire Nuffield Surgeons’ Trust (SWNST) ; Murphy, Paul|
|Format of File:|
|Extent:||184 leaves : ill., charts|
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