Adenosine metabolism and cancer. Focus on "Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatases and reducing ERK1/2 activity via a novel pathway".

ADENOSINE FACILITATES tumor survival by a variety of mechanisms. In this issue, Tan et al. (Ref. 16; see p. C433 of this issue) describe a signaling cascade by which adenosine downregulates the cell surface protein CD26 on HT-20 colorectal carcinoma cells. Because CD26 binds extracellular soluble adenosine deaminase (ADA) to the cell surface, this downregulation is expected to increase adenosine concentration in the microenvironment of the tumor cell membrane. This is one of several mechanisms by which tumors facilitate their own survival by influencing adenine nucleotide and adenosine metabolism and signaling. Adenosine accumulates in solid tumors and stimulates tumor growth and tumor angiogenesis while imparting tumor resistance to the immune system (15). Part of this resistance is due to adenosine signaling through A2A and possibly A2B adenosine receptors to inhibit the activation of macrophages (9, 10) and lymphocytes (6). Imiquimod, an immune system activator with anti-tumor activity, has recently been shown to block A2A receptors (14). This is consistent with the notion that adenosine in tumors suppresses the immune system.