Tumor associated macrophages and 'NO'

Nitric oxide (NO) and its pro and anti-tumor activities are dual roles that continue to be debated in cancer biology. The cell situations in the tumor and within the tumor microenvironment also have roles involving NO. In early tumorigenic events, macrophages in the tumor microenvironment promote tumor cell death, and later are reprogramed to support the growth of tumor, through regulatory events involving NO and several stimulatory signals. These two opposing and active phenotypes of tumor associated macrophages known as the M1 or anti-tumorigenic state and M2 or pro-tumorigenic state show differences in metabolic pathways such as glycolysis and arginine utilization, signaling pathways and cytokine induction including iNOS expression, therefore contributing to their function. Polarization of M2 to M1 macrophages, inhibition of M2 state, or reprogramming via NO in combination with other signals may determine or alter tumor kinetics. These strategies and an overview are presented.