VEGF-C及其受体VEGFR-3在胃癌淋巴转移中的作用

Role of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 in lymphatic metastasis of gastric carcinoma

目的:研究胃癌组织中血管内皮生长因子C(VEGF-C)及其受体3(VEGFR-3)的表达与淋巴管生成和淋巴结转移的关系,探讨其在胃癌淋巴转移中的作用和意义。方法:采用RT-PCR检测67例胃癌及正常胃组织中VEGF-C及VEGFR-3mRNA表达,酶组织化学方法行淋巴管染色并计数,同时分析胃癌淋巴结转移情况。结果:胃癌组织中VEGF-C及VEGFR-3 mRNA阳性表达分别为62.69%(42/67)、58.21%(39/67),显著高于在正常胃组织中的表达[23/67(34.3%)、21/67(31.3%),P<0.01],胃癌组织中两者表达有密切联系(P<0.01);在两者阳性表达的病例中,癌组织淋巴管计数和淋巴结转移显著增多(P<0.05或0.01)。结论:VEGF-C作用于VEGFR-3可诱导胃癌组织淋巴管生成,促进淋巴道转移;阻断两者信号转导、抑制胃癌淋巴管生成有望成为抗胃癌淋巴道转移治疗的新靶点。

Objective： To study expressions of vascular endothelial growth factor-C （VEGF-C） and vascular endothelial growth factor receptor-3（VEGFR-3） in gastric cancer tissues and the relationship between lymphangiogenesis and lymph node metastasis of gastric carcinoma, in an attempt to study the role of VEGF-C and VEGFR-3 in lymphatic metastasis. Methods：The expressions of VEGF-C and VEGFR 3 mRNA in 67 gastric carcinoma tissue specimens and their corresponding normal gastric tissues were determined by RT-PCR. Lymphatic vessels were stained by enzyme histochemicaI method and the lymph node metastasis of gastric carcinoma was analyzed according to pathological records. Results：The positive rates of VEGF-C and VEGFR- 3 mRNA in carcinoma tissues were significantly higher than those in normal gastric tissues （62.69% vs 34.3% and 58.21% vs 31.3%, respectively, both P〈0.01）. The expression of VEGF C was closely related to that of VEGFR 3 in gastric carcinoma （P〈0.01）. In patients with both VEGF-C and VEGFR-3 expressions, lymphatic vessels and lymph node metastasis were significantly increased compared with those in VEGF-C or VEGFR-3 negative cases（P〈0.05 or 0.01）. Conclusion： VEGF-C combined with VEGFR 3 may induce lymphangiogenesis and promote the lymph node metastasis of gastric carcinoma. The VEGF- C/VEGFR-3 signaling pathway may be a target for antilymphangiogenic therapy of gastric carcinoma.