TY - JOUR
T1 - Full-Length TrkB Variant in NSCLC Is Associated with Brain Metastasis
AU - Lombardi, Mariangela
AU - D'Ascanio, Michela
AU - Scarpino, Stefania
AU - Scozzi, Davide
AU - Giordano, Marco
AU - Costarelli, Leopoldo
AU - Raj, Enrico Rathina
AU - Mancini, Rita
AU - Cardillo, Giuseppe
AU - Cardaci, Vittorio
AU - Innammorato, Marta
AU - Vecchione, Andrea
AU - Ricci, Alberto
N1 - Publisher Copyright:
© 2020 Mariangela Lombardi et al.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
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U2 - 10.1155/2020/4193541
DO - 10.1155/2020/4193541
M3 - Article
C2 - 33294440
AN - SCOPUS:85097225777
VL - 2020
JO - BioMed Research International
JF - BioMed Research International
SN - 2314-6133
M1 - 4193541
ER -