Tumor-promoting functions of adenosine.

Tumor growth is a multifactorial process that, in addition to mutations leading to dysregulated expression of oncogenes and tumor suppressive genes, requires specific conditions that provide a supportive physiological environment at the primary and metastatic sites of the disease. Adenosine is one of the factors potentially contributing to tumor growth that thus far has not received adequate attention, despite evidence for a broad range of cytoprotective, growth-promoting, and immunosuppressive activities. Adenosine accumulates in solid tumors at high concentrations, and has been shown to stimulate tumor growth and angiogenesis and to inhibit cytokine synthesis, adhesion of immune cells to the endothelial wall, and the function of T-cells, macrophages, and natural killer cells. However, the mechanisms whereby adenosine accumulates in cancer and the specific effects that result from this accumulation are not well understood. This article surveys the available evidence that supports an important role of adenosine in cancer.