Neoneurogenesis and the neuro-neoplastic synapse.

A tumor is not an isolated entity within an organism, but tissue that strongly interacts with its environment. This interaction is however not restricted to direct cell-to-cell interactions, but generally comprises the susceptibility of tumor cells for chemokines and cytokines, as well as neurotransmitters and hormones by the expression of the according receptors. These signal substances have influences on tumor cell functions such as proliferation and migration. The other way round, tumor cells themselves release a broad range of these signal substances, which influence the cells of the environment. One of the first and most important interactions in this respect is the angiogenesis, which was discovered about 30 years ago. Tumor cells release angiogenic factors, i.e. the vascular endothelial growth factor as well as angiogenic chemokines among others. These factors initiate the vascularization of the tumor. Recently, a similar process was found for the development of lymphatic vessels in tumors. We herein seize these observations and combine them with arguments provided in the previous chapter, which leads us to the hypothesis that tumor cells may also be able to stimulate their own innervation; a process that we have termed neoneurogenesis.