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.