Research of anti-angiogenic/lymphangiogenic therapy in oral cancer targeting by Trks

Trk家族包括TrkA、TrkB和TrkC在癌症中的功能仍然未知。研究了Trks在口腔鳞状细胞癌（OSCC）中的作用。敲低Trks可抑制高表达Trks的OSCC细胞的生长或侵袭，减少细胞凋亡。VEGF表达与TrkA和TrkB表达相关;在TrkB敲低的OSCC细胞中观察到VEGF-C和VEGF-D的减少。TrkC不影响VEGF家族的表达。102例OSCC的免疫组化分析显示TrkB表达与微血管密度（MVD）、淋巴管密度（LVD）及预后不良有关。TrkC表达与临床分期、淋巴结转移、MVD、LVD及预后不良有关。TrkA表达与VEGF表达相关，而TrkB表达与VEGF、VEGF-C和VEGF-D的表达相关。TrkC和VEGF家族基因的表达之间没有发现显著的关联。在OSCC细胞中，Trks的表达与RUNX 3甲基化沉默相关。Trks表达与RUNX 3表达呈负相关。这些结果表明，Trks通过血管生成和淋巴管生成促进OSCC的进展。

The function of Trk family including TrkA, TrkB, and TrkC in cancer remains unknown. The role of Trks in oral squamous cell carcinoma (OSCC) was examined. Knockdown of Trks provided inhibition of growth or invasion and decrease of apoptosis in OSCC cells, which expressed Trks at high levels. VEGF expression was associated with TrkA and TrkB expression; a decrease of VEGF-C and VEGF-D was observed in OSCC cells with TrkB knockdown. TrkC did not affect the expression of VEGF family. An immunohistochemical analysis of 102 OSCCs showed that TrkB expression was related to microvessel density (MVD), lymph vessel density (LVD), and poor prognosis. TrkC expression was correlated with clinical stage, lymph node metastasis, MVD, LVD, and poor prognosis. TrkA expression was associated with VEGF expression, whereas TrkB expression was associated with the expressions of VEGF, VEGF-C and VEGF-D. No significant association was found between the expression of TrkC and genes of the VEGF family. Expression of Trks was associated with RUNX3 silencing by methylation in OSCC cells. Trks expression was inversely correlated with RUNX3 expression in the OSCC cases. These results suggested that Trks enhances progression of OSCC through angiogenesis and lymphangiogenesis.