Full-Length TrkB Variant in NSCLC Is Associated with Brain Metastasis

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotroph...

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Published in:	BioMed research international 2020, Vol.2020, p.4193541-7
Main Authors:	Lombardi, Mariangela, D'Ascanio, Michela, Scarpino, Stefania, Scozzi, Davide, Giordano, Marco, Costarelli, Leopoldo, Raj, Enrico Rathina, Mancini, Rita, Cardillo, Giuseppe, Cardaci, Vittorio, Innammorato, Marta, Vecchione, Andrea, Ricci, Alberto
Format:	Article
Language:	eng
Subjects:	Aged Analysis Antibodies Biopsy Brain Brain Neoplasms - genetics Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Cancer therapies Carcinoma, Non-Small-Cell Lung - genetics Care and treatment Cell Adhesion Cell Line, Tumor Central nervous system Female Gene Expression Regulation, Neoplastic Genetic aspects Growth factors Humans Identification and classification Immunohistochemistry Kinases Lung cancer Lung cancer, Non-small cell Lung Neoplasms - genetics Male Metastases Metastasis Middle Aged Mutation Mutation - genetics Nervous system Non-small cell lung carcinoma Patients Phosphotransferases Properties Protein-tyrosine kinase Receptor, trkB - genetics Receptor, trkB - metabolism Receptors Small cell lung carcinoma Spheroids, Cellular - metabolism Spheroids, Cellular - pathology Statistical methods TrkB receptors Tyrosine
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Summary:	Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their expression was related to preferential tumor entry into the central nervous system (CNS). By immunohistochemistry, 80% of the ADKs that metastasize to central nervous system expressed TrkB receptor compared to 33% expressing of ADKs without CNS metastasis. Moreover, ADKs with CNS metastasis showed an elevated expression of the full-length TrkB receptor. The TrkB receptor FL/T1 ratio was statistically higher in primary ADKs with brain metastasis compared to ADKs without brain metastasis. Our data indicate that TrkB full-length isoform expression in primary ADK cells may be associated with higher risk to develop brain metastasis. Therefore, TrkB receptor may possess prognostic and therapeutic implications in lung ADK.
ISSN:	2314-6133 2314-6141