Antineoplastic drugs modulate CXCR4 and CD26 cell-surface expression and function on colorectal carcinoma cells.
Date
2007
Authors
Lowthers, Erica Lauren.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
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.
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.
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.
Thesis (Ph.D.)--Dalhousie University (Canada), 2007.
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.
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.
Thesis (Ph.D.)--Dalhousie University (Canada), 2007.
Keywords
Health Sciences, Pharmacology.