| dc.contributor.author | Lowthers, Erica Lauren. | en_US |
| dc.date.accessioned | 2014-10-21T12:33:50Z | |
| dc.date.available | 2007 | |
| dc.date.issued | 2007 | en_US |
| dc.identifier.other | AAINR31500 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/54963 | |
| dc.description | CXCR4 is the cell-surface receptor for the chemokine CXCL12; CXCR4-bearing cells tend to localize in CXCL12-secreting tissues, a process that is essential for normal cellular trafficking in contexts such as hematopoiesis. An increase in CXCR4 expression has been observed in a range of cancers, and correlates with poor clinical outcome as this facilitates tumour cell migration to and/or expansion at CXCL12-rich metastatic sites. We show that treating cells with each of several anticancer drugs (5-fluorouracil, cisplatin, vinblastine or methotrexate) down-regulates cell-surface CXCR4 protein, leading to a corresponding decrease in cellular migration toward CXCL12. | en_US |
| dc.description | CD26 is another cell-surface molecule that has been implicated in the metastatic process. CD26 is important for cell-to-cell adhesion and binding of adenosine deaminase (ADA). Furthermore, CD26 has dipeptidyl peptidase IV (DPPIV) activity which cleaves certain chemokines, including CXCL12, thus reducing the migratory potential of CXCR4-expressing cells. CD26 is often down-regulated in cancer and a decline in CD26 has been correlated with increased invasion, migration, and enhanced morbidity in rodent tumor models. We show that treatment of cells with anticancer drugs leads to an up-regulation of CD26 at the cell-surface and an increase in DPPIV activity and ADA-binding capacity in vitro. These drugs also up-regulate CD26 expression in an in vivo orthotopic model of colorectal carcinoma. | en_US |
| dc.description | Therefore, treatment of colorectal carcinoma cells with diverse anticancer drugs causes changes in the expression of CXCR4 and CD26 that would correspond to a reduced metastatic potential of the tumor cells. This suggests that it may be possible to use anticancer drugs to reduce metastatic spread. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2007. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.title | Antineoplastic drugs modulate CXCR4 and CD26 cell-surface expression and function on colorectal carcinoma cells. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
