The Role of Neural Signaling in the Pancreatic Cancer Microenvironment

SIMPLE SUMMARY: Pancreatic cancer is a highly lethal malignant disease with a dense stroma, called the tumor microenvironment. Accumulating evidence indicates the important role of sympathetic, parasympathetic, and sensory nerves in the tumor microenvironment of various cancers, including pancreatic cancer. Cancer cells and neural cells interact with each other to form a complex network and cooperatively promote cancer growth and invasion. In this review article, we describe the current understanding of the role of nerves in the tumor microenvironment. ABSTRACT: Pancreatic cancer is one of the most lethal malignant diseases. Various cells in the tumor microenvironment interact with tumor cells and orchestrate to support tumor progression. Several kinds of nerves are found in the tumor microenvironment, and each plays an essential role in tumor biology. Recent studies have shown that sympathetic, parasympathetic, and sensory neurons are found in the pancreatic cancer microenvironment. Neural signaling not only targets neural cells, but tumor cells and immune cells via neural receptors expressed on these cells, through which tumor growth, inflammation, and anti-tumor immunity are affected. Thus, these broad-range effects of neural signaling in the pancreatic cancer microenvironment may represent novel therapeutic targets. The modulation of neural signaling may be a therapeutic strategy targeting the whole tumor microenvironment. In this review, we describe the current understanding of the role of nerves in the tumor microenvironment of various cancers, with an emphasis on pancreatic cancer. We also discuss the underlying mechanisms and the possibility of therapeutic applications.