Fig. 4.
Molecular mechanisms of perineural invasion (PNI). PNI results from multidirectional signaling between the cancer and the nerve microenvironment involving various signaling and cellular adhesion molecules. BDNF, brain-derived neurotrophic factor; COX2, cyclooxygenase-2; CSF1, colony stimulating factor 1; CSF1R, colony stimulating factor 1 receptor; ECM, extracellular matrix; GAL; galanin; GDNF, glial cell line-derived neurotrophic factor; GFRα, GDNF receptor-α; L1CAM, L1 cell adhesion molecule; MAG, myelin-associated glycoprotein; MMP, matrix metalloproteinase; NCAM, neural cell adhesion molecule; NGF, nerve growth factor; NT3, neurotrophin-3; PGE2, prostaglandin E2.