Am. J. Respir. Cell Mol. Biol., Volume 25, Number 4, October, 2001 439-446

Neurotrophins and Neurotrophin Receptors in Human Lung Cancer

Alberto Ricci, Stefania Greco, Salvatore Mariotta, Laura Felici, Elena Bronzetti, Andrea Cavazzana, Giuseppe Cardillo, Francesco Amenta, Alberto Bisetti, and Giuseppe Barbolini

Dipartimento di Scienze Cardiovascolari e Respiratorie, Università "La Sapienza," Rome, Servizio di Anatomia Patologica and Unità Operativa di Chirurgia Toracica, Ospedale Carlo Forlanini Rome; Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, Camerino; and Istituto di Anatomia Patologica, Università di Modena, Modena, Italy

The expression of neurotrophins (NTs) and related high- and low-affinity receptors was studied in surgical samples of histologically diagnosed human tumors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer specimens by Western blot analysis and immunohistochemistry to assess expression and distribution of NT and NT receptor proteins in tissues examined. Immunoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 antibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than those displayed by human -NGF and proteins from rat brain. A specific immunoreactivity for NTs and NT receptors was demonstrated in vessel walls, stromal fibroblasts, immune cells, and sometimes within neoplastic cell bodies. Approximately 33% of bronchioloalveolar carcinomas exhibited a strong membrane NGF and TrkA immunoreactivity, whereas 46% adenocarcinomas expressed an intense TrkA immunoreactivity but a weak immunostaining for NGF within tumor cells. Moreover, squamous cell carcinomas developed an intense TrkA immunoreactivity only within stroma surrounding neoplastic cells. A faint BDNF and TrkB immunoreactivity was documented in adenocarcinomas, squamous cell carcinomas, and small cell lung cancers. NT-3 and its corresponding TrkC receptor were found in a small number of squamous cell carcinomas within large-size tumor cells. No expression of low-affinity p75 receptor protein was found 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 controlling growth and differentiation of human lung cancer and/or influencing tumor behavior.

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