Smad4的表达与胰腺癌淋巴管生成之间的关系

Correlation of Smad4 expression with lymphangiogenesis in pancreatic cancer

目的观察血管内皮生长因子(VEGF)-C和Smad 4在胰腺癌组织内的表达情况,分析VEGF-C和Smad 4的表达与胰腺癌淋巴管生成及淋巴结转移之间的关系。方法取胰腺癌病例52例,其中,无淋巴结转移组12例,淋巴结转移组40例。应用免疫组化和Western blot技术检测VEGF-C和Smad4在胰腺癌组织内的表达情况。以D2-40作为淋巴管内皮标记物,观察胰腺癌组织内淋巴管生成情况。结果 VEGF-C主要表达于胰腺癌细胞胞质内,在淋巴结转移组的表达水平明显高于无淋巴结转移组。Smad4表达于胰腺癌细胞胞质和胞核内,在无淋巴结转移组的表达水平明显高于淋巴结转移组,Smad4表达阳性组淋巴管数密度明显低于Smad4表达阴性组(=0.02)。Smad4的表达与VEGF-C的表达呈显著的负相关性。结论 VEGF-C在胰腺癌淋巴管的发生及淋巴结转移中发挥重要作用,Smad4可能通过调节VEGF-C蛋白的表达抑制胰腺癌淋巴管生成和淋巴结转移。

Objective To investigate the effects of vascular endothelial growth factor （VEGF）-C and Smad4 on lymphangiogenesis and lymph node metastasis, we observed the expression of VEGF-C and Smad4 in pancreatic cancer. Methods Fifty-two specimens from patients with pancreatic cancer were included in this study. Among all of 52 specimens, they were divided into lymph node metastatic group（n=40） and nonmetastatic group（n=12）. The expressions of ~EGF-C and Smad4 were detected by immunohistochemical stain and Western blot. D2-40 was used as the specific lymphatic endothelial marker for detecting lymphangiogenesis in pancreatic cancer. Results VEGF-C protein was observed predominantly in the cytoplasm of the tumor cells, the expression of VEGF-C in lymph node metastatic group was significantly higher than that in nonmetastatic group. Smad4 protein was observed in cytoplasm and nucleus of tumor cells, the expression of Smad4 in nonmetastatic group was significantly higher than that in lymph node metastatic group in immunohistoehemical slain and Western blot analysis respectively. The lymphatic vessel density（LVD） in Smad4 positive group was significantly decreased than that in Smad4 negative ggoup（ p =0.02）. Smad4 expmssian was negative correlated with VEGF-C expression. Conclusion VEGF-C plays an important role in tumor lymphangiogenesis and lymph node metastasis in pancreatic cancer. Smad4 expression showed negative correlation with VEGF-C expression. Smad4 may regulate the expression of VEGF-C protein in pancreatic cancer. This indicated that Smad4 may play an important role in tumor lymphangiogenesis and lymph node metastasis.