Figure 1.

An illustration of the multiple means of pathogenesis involved in cancer–nerve crosstalk: (a) Macrophages, Schwann cells, fibroblasts, immunocytes, and other stroma cells have been reported to be involved in perineural invasion (PNI), where multiple neurotropic, neuroadhesion, axon guidance factors, neurotransmitters/neuropeptides, and cytokines/chemokines participate in cellular interactions; (b) Induced and promoted by cancer cells, neuritogenesis promotes tumorigenesis and cancer progression by directly activating cancer cells or inducing angiogenesis, modulating the immunomicroenviornment, and so forth through means of multiple neurotransmitters or neuropeptides. Neoneurogenesis occurs when neural progenitors (or, in some instances, cancer stem cells) differentiate to mature neurons and is followed by tumor-induced neuritogenesis. rSC: repair Schwann cell (or dedifferentiated Schwann cell); dSC: differentiated Schwann cell; NGF: neural growth factor.