Cargando…

Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer

Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (C...

Descripción completa

Detalles Bibliográficos
Autores principales: Tanaka, Koji, Okugawa, Yoshinaga, Toiyama, Yuji, Inoue, Yasuhiro, Saigusa, Susumu, Kawamura, Mikio, Araki, Toshimitsu, Uchida, Keiichi, Mohri, Yasuhiko, Kusunoki, Masato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011754/
https://www.ncbi.nlm.nih.gov/pubmed/24801982
http://dx.doi.org/10.1371/journal.pone.0096410
_version_ 1782314837732229120
author Tanaka, Koji
Okugawa, Yoshinaga
Toiyama, Yuji
Inoue, Yasuhiro
Saigusa, Susumu
Kawamura, Mikio
Araki, Toshimitsu
Uchida, Keiichi
Mohri, Yasuhiko
Kusunoki, Masato
author_facet Tanaka, Koji
Okugawa, Yoshinaga
Toiyama, Yuji
Inoue, Yasuhiro
Saigusa, Susumu
Kawamura, Mikio
Araki, Toshimitsu
Uchida, Keiichi
Mohri, Yasuhiko
Kusunoki, Masato
author_sort Tanaka, Koji
collection PubMed
description Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with K252a, peritoneal metastatic nodules was found to be reduced, as compared with control mice. BDNF/TrkB signaling may thus be a potential target for treating peritoneal carcinomatosis arising from colorectal cancer.
format Online
Article
Text
id pubmed-4011754
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40117542014-05-09 Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer Tanaka, Koji Okugawa, Yoshinaga Toiyama, Yuji Inoue, Yasuhiro Saigusa, Susumu Kawamura, Mikio Araki, Toshimitsu Uchida, Keiichi Mohri, Yasuhiko Kusunoki, Masato PLoS One Research Article Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with K252a, peritoneal metastatic nodules was found to be reduced, as compared with control mice. BDNF/TrkB signaling may thus be a potential target for treating peritoneal carcinomatosis arising from colorectal cancer. Public Library of Science 2014-05-06 /pmc/articles/PMC4011754/ /pubmed/24801982 http://dx.doi.org/10.1371/journal.pone.0096410 Text en © 2014 Tanaka et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tanaka, Koji
Okugawa, Yoshinaga
Toiyama, Yuji
Inoue, Yasuhiro
Saigusa, Susumu
Kawamura, Mikio
Araki, Toshimitsu
Uchida, Keiichi
Mohri, Yasuhiko
Kusunoki, Masato
Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer
title Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer
title_full Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer
title_fullStr Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer
title_full_unstemmed Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer
title_short Brain-Derived Neurotrophic Factor (BDNF)-Induced Tropomyosin-Related Kinase B (Trk B) Signaling Is a Potential Therapeutic Target for Peritoneal Carcinomatosis Arising from Colorectal Cancer
title_sort brain-derived neurotrophic factor (bdnf)-induced tropomyosin-related kinase b (trk b) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011754/
https://www.ncbi.nlm.nih.gov/pubmed/24801982
http://dx.doi.org/10.1371/journal.pone.0096410
work_keys_str_mv AT tanakakoji brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT okugawayoshinaga brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT toiyamayuji brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT inoueyasuhiro brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT saigusasusumu brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT kawamuramikio brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT arakitoshimitsu brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT uchidakeiichi brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT mohriyasuhiko brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer
AT kusunokimasato brainderivedneurotrophicfactorbdnfinducedtropomyosinrelatedkinasebtrkbsignalingisapotentialtherapeutictargetforperitonealcarcinomatosisarisingfromcolorectalcancer