Growth-Promoting and Angiogenic Functions of Adenosine in Breast Cancer

摘要

Adenosine is a potential novel factor in breast cancer progression and this project has been designed to evaluate local adenosine tumor-promoting activity experimentally. We have aimed at testing growth and angiogenic properties of cells that differ in adenosine production rates in xenograft model using immunocompromized mice. During the 3-year period we have accomplished several specific goals successfully. We have generated cell variants that differ in their capacity to produce endogenous adensine. We have determined that their growth rate as xenografts depends on the number of cells injected orthotopically into mice. At 2.5 x 106 cells per site we have seen decreased growth of eN(-) cells. In addition, we have demonstrated that eN specifically interacts with Tenascin C and cells with suppressed eN expression have enhanced motility on Tenascin C. Furthermore, using protein expression profiling we have determined that high eN expression coincides with mesenchymal phenotype and that HDAC inhibitor TSA reverses epithelial expression profile in breast cancer cells. However some goals have not been accomplished within the proposed time frame. Given the importance of proposed research we are continuing our work toward accomplishing these goals using other funding sources.