In the genomic era of
cancer research, the development of
metastases has been attributed to mutations in the
tumor that enable the cells to migrate. However, gene analyses revealed that primary
tumors and
metastases were in some cases genetically identical and the question was raised whether
metastasis formation might be an inherent feature of certain
tumor cells. In contradiction to this view, the last decade of
cancer research has brought to light, that
tumor cell migration, similar to leukocyte and fibroblast migration, is a highly regulated process. The nervous system plays an important role in this regulation, at least in two respects: firstly,
neurotransmitters are known to regulate the migratory activity of
tumor cells, and secondly, nerve fibers are used as routes for perineural invasion. We also summarize here the current knowledge on the innervation of
tumors. Such a process might establish a neuro-neoplastic synapse, with the close interaction of
tumor cells and nerve cells supporting
metastasis formation.