Inducting or Accessing Vasculature

All solid tumors require adequate vascular supply for their growth, which they achieve by induction of (neo)angiogenesis. This is a complex process occurring at the level of the tumor microenvironment, involving tumor and nontumor cells and their secreted substances such as cytokines, growth factors, extracellular matrix, and microvesicles (De Palma et al. 2017). The secretion of these proangiogenic substances is regulated by, among others, neurotransmitters that are released in the tumor microenvironment. Some neurotransmitters, such as norepinephrine and neuropeptide Y, have a stimulatory effect on angiogenesis, while others, such as dopamine, inhibit it. Others, such as acetylcholine, may act either stimulatory or inhibitory, depending on the type of cholinergic receptors activated.