Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan, ROC.
Int J Oncol. 2010 Oct;37(4):943-9. doi: 10.3892/ijo_00000745.
BDNF (brain-derived neurotrophic factor) and its receptor TrkB (tropomyosin receptor kinase B) play important roles in the progression of cancer, including transitional cell carcinoma (TCC) cells reported in our previous investigation. In this study, we used a specific TrkB antibody (Ab) to evaluate its effects on survival, proliferation and migration/invasion in three TCC cell lines (BFTC905, T24 and TSGH8301) in vitro. The TrkB Ab at 1 and 3 microg/ml, but not the TrkA or TrkC Abs, significantly elicited cytotoxicity in TCC cells. The TrkB Ab at 3 microg/ml also induced apoptosis of TCC cells, which may result from up-regulation of phospho-p38 plus down-regulation of survivin and securin expression. The TrkB Ab at 0.5 microg/ml, which did not show cytotoxicity, suppressed migration of TCC cells and invasion of BFTC905 cells, possibly mediated through increased E-cadherin, decreased BDNF-stimulated phospho-PLCgamma1 and reduced MMP-9 activity. These results indicate that TrkB blockade may be a new strategy for TCC therapy.
脑源性神经营养因子（BDNF）及其受体 TrkB（原肌球蛋白受体激酶 B）在癌症的进展中发挥着重要作用，包括我们之前的研究中报道的移行细胞癌（TCC）细胞。在这项研究中，我们使用了一种特异性的 TrkB 抗体（Ab）来评估其对三种 TCC 细胞系（BFTC905、T24 和 TSGH8301）体外生存、增殖和迁移/侵袭的影响。1 和 3 μg/ml 的 TrkB Ab，但不是 TrkA 或 TrkC Ab，显著地引起了 TCC 细胞的细胞毒性。3 μg/ml 的 TrkB Ab 也诱导了 TCC 细胞的凋亡，这可能是由于磷酸化 p38 的上调和生存素和 securin 表达的下调所致。0.5 μg/ml 的 TrkB Ab 没有表现出细胞毒性，但抑制了 TCC 细胞的迁移和 BFTC905 细胞的侵袭，可能是通过增加 E-钙黏蛋白、减少 BDNF 刺激的磷酸化 PLCγ1 和降低 MMP-9 活性来介导的。这些结果表明，TrkB 阻断可能是 TCC 治疗的一种新策略。
