Increased expression of autotaxin has been shown to promote metastasis formation and cancer proliferation. These actions could be related to the catalytic activity of autotaxin which converts lysophosphatidylcholine into lysophosphatidate extracellularly or non-catalytic functions of autotaxin may be responsible. Also both LPC and LPA have been reported to stimulate migration through their respective receptors. This work investigates the role of autotaxin in controlling the motility of two cancer cell lines. With the use of autotaxin inhibitors we were able to block LPC-induced migration. Knocking-down autotaxin secretion also blocked stimulation of migration by LPC. Autotaxin
inhibitors abolished any migratory effects from media collected from autotaxin secreting cells. We determined that LPC alone is unable to stimulate migration. Also we did not observe non-catalytic effects of autotaxin on migration. This thesis provides strong evidence that the inhibition of autotaxin production or activity would provide a beneficial therapy in the prevention of tumour growth or metastasis in patients with autotaxin expressing tumours.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1058 |
| Date | 06 1900 |
| Creators | Gaetano, Cristoforo Giuseppe |
| Contributors | Dr. Brindley, David N. (Biochemisty), Dr. Holmes, Charles F. (Biochemisty), Dr. Michalak, Marek (Biochemistry), Dr. McMullen, Todd (Medicine) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 2628196 bytes, application/pdf |
| Relation | Gaetano, C.G. (2009). http://www3.interscience.wiley.com/journal/122186183/abstract?CRETRY=1&SRETRY=0 |
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