Neurotrophins and neurotrophin receptors in human lung cancer

The expression of neurotrophins (NTs) and related high- and low-affinity re ceptors was studied in surgical samples of histologically diagnosed human t umors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer sp ecimens by Western biot analysis and immunohistochemistry to assess express ion and distribution of NT and NT receptor proteins in tissues examined. Im munoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 ant ibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than t hose displayed by human P-NGF and proteins from rat brain. A specific immun oreactivity for NTs and NT receptors was demonstrated in vessel wails, stro mal fibroblasts, immune cells, and sometimes within neoplastic cell bodies. Approximately 33% of bronchioloalveolar carcinomas exhibited a strong memb rane NGF and TrkA immunoreactivity, whereas 46% adenocarcinomas expressed a n intense TrkA immunoreactivity but a weak immunostaining for NGF within tu mor cells. Moreover, squamous cell carcinomas developed an intense TrkA imm unoreactivity only within stroma surrounding neoplastic cells. A faint BDNF an Tr immunoreactivity was documented in adenocarcinomas, squamous cell ca rcinomas, and small cell lung cancers. NT-3 and its corresponding TrkC rece ptor were found in a small number of squamous cell carcinomas within large- size tumor cells. No expression of low-affinity p75 receptor protein was fo und in tumor cells. The detection of NTs and NT receptor proteins in tumors of the lower respiratory tract suggests that NTs may be involved in contro lling growth and differentiation of human lung cancer and/or influencing tu mor behavior.