The role of adenosine in tumor microenvironment

Adenosine, an endogenous purine nucleoside, is ubiquitously found in both intracellular and extracellular spaces. It plays an important role in various physiological and pathophysiological conditions. Extracellular adenosine is known as a homeostatic molecule in nanomolar range (20–200 nM); but its concentration is increased up to 1000–10,000 nM in pathological conditions such as canceras a result of hypoxia which leading to progression of tumor in different ways through its G-coupling receptors including A1, A2a A2b and A3 adenosine receptors. They found in Tumor microenvironment (TME) cells including cancer cells, immune cells stroma cells and endothelial cells. Hypoxia by up-regulating of CD-39 and CD-73 ecto-nucleotidases increases the extracellular level of adenosine in solid tumors. The most effect of adenosine in TME is local immune suppression. It has been shown adenosine creates an immune-tolerant tumor microenvironment by regulating the functions of immune and inflammatory cells, such as macrophages, dendritic cells, myeloid-derived suppressor cells, T cells and natural killer (NK) cells. At very high concentrations of adenosine, cells may be triggered to undergo apoptosis, although some tumor cells are resistant to this action of adenosine. Adenosine acts on isolated cancer cell populations to increase cell motility, adhesion to the extracellular matrix, the expression of cell attachment proteins and receptors for molecules that can direct cell movement. Adenosine also is able to promote endothelial cell division and motility, and has been shown to enhance the angiogenesis via up- regulating of VEGF factor. Modulation of local adenosine has been demonstrated as efficient strategy to control progression of solid tumor so that monoclonal antibody against CD-73 ecto-nucleotidase, a key enzyme in metabolism of extracellular adenosine currently undergoing Phase I clinical trials in breast cancer. extracellular adenosine bursting in hypoxic niche of tumor leading to unfavorable pathologic condition which resulting in progression of cancer. Suppressing adenosine production pathway or inhibition of its signaling pathway proposed in various studies to inhibit tumor progression.

Keywords:

Breast Cancer , Cell and Cancer , Solid Tumors , Cancer Treatment and Management , Drugs and Cancer