VEGF-C及其受体VEGFR-3在胃癌淋巴转移中的作用

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-3 mRNA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.

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

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 histochemical 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.