Adenosine down-regulates the surface expression of dipeptidyl peptidase IV on HT-29 human colorectal carcinoma cells: implications for cancer cell behavior.

摘要: Dipeptidyl peptidase IV (DPPIV) is a multifunctional cell-surface protein that, as well having dipeptidase activity, the major binding for adenosine deaminase (ADA) and also binds extracellular matrix proteins such fibronectin collagen. It typically reduces activity of chemokines other peptide mediators result its enzymatic activity. DPPIV aberrantly expressed in many cancers, decreased expression has been linked to increases invasion metastasis. We asked whether adenosine, purine nucleoside that present at increased levels hypoxic tumor microenvironment, might affect cell surface. Treatment with single dose produced an initial transient (1 4 hours) modest (∼10%) increase DPPIV, followed by more profound (∼40%) depression surface HT-29 human colon carcinoma cells, maximal decline being reached after 48 hours, persisting least week daily exposure adenosine. This down-regulation occurred concentrations comparable those within fluid colorectal tumors growing vivo, was not elicited inosine or guanosine. Neither cellular uptake nor phosphorylation necessary DPPIV. The decrease paralleled decreases enzyme ADA, ability cells bind migrate on fibronectin. Adenosine, exist solid tumors, therefore acts activities may sensitivity cancer tumor-promoting effects their response matrix, facilitating expansion