Neurotrophin system expression in human pulmonary carcinoid tumors

Neurotrophin (NT) and NT receptor expression was assessed in 12 typical (TC) and 8 atypical (AC) human pulmonary carcinoids by Western blot and immunohistochemistry. TC and AC carcinoid express to different extent NT and NT receptor proteins. Nerve growth factor (NGF) was expressed by 83% of the TC but not by the AC carcinoids. Brain derived neurotrophic factor (BDNF) was expressed by 33 and 100% of TC and AC carcinoids, respectively. NT-3 was expressed by 58% of the TC and 38% of AC carcinoids. TC carcinoids express high affinity NT receptors while 50% of the AC carcinoids express the TrkB receptor. Our results demonstrate that NGF/TrkA and BDNF/TrkB signaling need to be considered as regulatory pathways that may address survival, differentiation and/or aggressiveness of human pulmonary carcinoids. Contrarily to the BDNF/TrkB, expression of the NGF/TrkA signaling may overcome aggressiveness of carcinoid cells. NTs may be useful as markers in the clinic.