Cancer tumor development is the product of interactions between (1) genetically altered pre-cancerous epithelial stem cell and (2) its altered stromal microenvironment, including (a) bone marrow derived myofibroblasts (cancer associated fibroblasts), (b) tumor associated macrophages, and (c) some other altered stromal cells. Signals from the altered stromal cells promote epigenetical transformation of the pre-cancerous cell into a cancer cell, increase cancer cell invasive and metastatic capabilities, and promote neoangiogenesis. Together with the signals coming from the tumor cells, the stromal signals also trigger neoangiogenesis that is important for tumor existence and development. Stromal alterations that trigger pre-cancerous cell transformation may be a result of chronic inflammation. Inflammation also promotes migration of mast cells, mesenchymal stem cells and other neuroendocrine cells into the inflammation area. Neuroendocrine cells of the tumor and neurons that innervate the tumor secrete neurotransmitters. These neurotransmitters may increase cancer drug resistance and promote tumor growth and metastasis. This means that signaling molecules secreted by the neurons into the tumor matrix [alongside with some other molecules involved in cell communication e.g. cytokines and non-coding RNAs] support tumor integrity and stability. If the cell communication is interrupted, the tumor becomes less aggressive and more sensitive to the therapeutic agents. The use of neurotransmission antagonists as a potential novel therapeutic strategy against human cancer is worth exploring through clinical trials.

Keywords:
Stromal-epithelial interaction, tumor microenvironment, nerve-cancer interaction, neurotransmitters, neurotransmitters, neurotransmitter agonists, neurotransmitter antagonists.