Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma

Abstract

Members of the tropomyosin receptor kinase (Trk) family have a high affinity for neurotrophins and regulate neuronal survival. The role of Trks in cancer is still controversial. The expression and role of TrkB and TrkC were examined in colorectal cancer (CRC). Immunohistochemical analysis of TrkB and TrkC was performed in 133 patients with CRC. Using human CRC cell lines, expression of vascular endothelial growth factor (VEGF) and transforming growth factor β, cell growth, invasion, and apoptosis were examined by knockdown methods. Immunohistochemistry showed positive results of TrkB and TrkC (23.3% and 12.8%, respectively). TrkB expression was associated with local progression (P = .0284), clinical stage (P = .0026), nodal metastasis (P = .0068), and peritoneal metastasis (P = .0026). TrkC expression was only related to liver metastasis (P = .0001). Coexpression of TrkB or TrkC and their ligands was found in 80.6% and 82.4% of cases, respectively. In vitro analysis using human CRC cells showed that TrkB positively regulated gene expression of VEGF-A (P < .05) and VEGF-C (P < .05), whereas TrkC suppressed transforming growth factor β expression (P < .05). TrkB and TrkC induced cell growth (P < .05) and invasion (P < .05), respectively. Both TrkB and TrkC showed antiapoptotic effect (P < .05). These results suggest that TrkB and TrkC have a tumor progressive function and may be a useful diagnostic and therapeutic target in CRC.