Nitric oxide (NO) is a radical species that have been implicated in vasodilation, neuronal signaling, immunology, and cancer. In cancer, NO functions in various and sometimes contradictory signaling pathways within the tumor microenvironment (TME). For example, high nitric oxide synthase expressions in activated macrophages exert cytostatic or cytotoxic effects.
On the other hand, resident macrophages within the TME tend to produce low steady-state concentrations of NO and are associated with a more aggressive phenotype as well as a poorer clinical prognosis, which may be important in the context of cancer prevention and treatment.
In a recently published study, researchers have found a link between increased nitric oxide levels where tumors develop and the consumption of high-fat diets.
To observe the NO on a molecular level, the team developed a molecular probe that can produce images deep inside body tissues, called BL660-NO, and used a mice model.
The researchers used breast cancer-carrying BALB/c mice, who ate a high-fat diet in which 60% of calories came from fat. The mice became obese and developed large tumors. On the other hand, the control group was fed a low-fat diet of only 10% of the total calories.
The team observed that NO was required in a tumor microenvironment, with a low concentration supporting tumor growth, proliferation, and metastasis, whereas high concentrations killed cancer cells through DNA damage and nitrosative stresses.
Their results also showed that an inflammatory diet increased NO production via recruitment of macrophages and overexpression of nitric oxide synthase, driving tumor progression.
Anuj K. Yadav, et al. Activity-Based NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide. ACS Cent. Sci. 2022, 8, 4, 461–472. https://doi.org/10.1021/acscentsci.1c00317