BANCR调控VEGF-C/VEGFR-3通路促进胰腺癌微淋巴管生成

BANCR promoting lymphangiogenesis by regulating VEGF-C/VEGFR-3 pathway in pancreatic cancer

目的研究BANCR在胰腺癌中的表达及其对淋巴管生成作用机制。方法实时荧光定量PCR(qPCR)检测胰腺癌细胞(SW1990、PANC-1)及人胰腺导管上皮细胞(HPDC)中BANCR的表达;应用siRNA干扰胰腺癌细胞BANCR的表达,将转染后的胰腺癌细胞与人真皮淋巴管内皮细胞(HDLEC)进行3D共培养,并统计微淋巴管密度(MLVD)。应用qPCR检测转染后的BANCR-siRNA组和空载质粒NC组胰腺癌细胞中VEGF-C、VEGFR-3 mRNA的相对表达量。结果与HPDC的1.02±0.222相比,胰腺癌细胞PANC-1和SW1990中BANCR显著高表达,分别为10.03±3.356、10.37±1.459(P<0.001)。干扰BANCR表达后BANCR-siRNA组的胰腺癌细胞MLVD较NC组显著降低(SW1990:3.87±1.767 vs 18.00±6.130,P<0.001;PANC-1:5.27±2.631 vs 16.80±3.764,P<0.001)。且BANCR-siRNA组中VEGF-C及VEGFR-3转录水平较NC组显著下调(VEGF-C:1.35±0.926 vs 6.97±3.677,P=0.011;VEGFR-3:0.98±0.635 vs 2.88±1.422,P=0.026)。结论BANCR在胰腺癌细胞中表达上调,并可能通过调控VEGF-C/VEGFR-3通路促进胰腺癌淋巴管生成和淋巴结转移,有望为胰腺癌的诊治提供新靶点。

Objective To investigate the expression of BANCR in pancreatic carcinoma and its mechanism on lymphangiogenesis.Methods The expression of BANCR in pancreatic cancer cells(SW1990,PANC-1)and human pancreatic ductal epithelial cell(HPDC)was detected by qPCR.siRNA was used to interfere with the expression of BANCR in pancreatic cancer cells.The transfected pancreatic cancer cells and human dermal lymphatic endothelial cells(HDLEC)were co-cultured in 3D,and micro-lymphatic vessel density(MLVD)was calculated.qPCR was used to detect the relative expression of VEGF-C and VEGFR-3 mRNA in pancreatic cancer cells of BANCR-siRNA group and NC group.Results Compared with 1.02±0.222 of HPDC,the expression of BANCR in PANC-1 and SW1990 cells was significantly higher(10.03±3.356,10.37±1.459,respectively)(P<0.001).The pancreatic cancer cell MLVD in the BANCR-siRNA group was significantly lower than that in the NC group(SW1990:3.87±1.767 vs 18.00±6.130,P<0.001;PANC-1:5.27±2.631 vs 16.80±3.764,P<0.001).And the transcriptional level of VEGF-C and VEGFR-3 in the BANCR-siRNA group was significantly lower than that in the NC group(VEGF-C:1.35±0.926 vs 6.97±3.677,P=0.011;VEGFR-3:0.98±0.635 vs 2.88±1.422,P=0.026).Conclusion BANCR is up-regulated in pancreatic carcinoma cells and may play an important role in lymphangiogenesis and lymph node metastasis in pancreatic carcinoma by regulating VEGF-C/VEGFR-3 pathway,which is expected to provide a new target for clinical diagnosis,treatment and prognosis of pancreatic carcinoma.