Deng Jingyu, Cui Jingli, Jiang Nan, Zhang Rupeng, Zhang Li, Hao Xishan, Liang Han
Department of Gastroenterology, Tianjin Medical University Cancer Hospital and City Key Laboratory of Cancer Prevention and Therapy, Nation Clinical Center of Cancer Tianjin, China.
Am J Transl Res. 2014 Nov 22;6(6):756-67. eCollection 2014.
To explore the potential mechanism of vascular endothelial growth factor D (VEGF-D) contribution to the lymphangiogenesis was regulated by the signal transducer and activator of transcription 3 (STAT3).
We detected the expression in GC tissue, adjacent non-tumor tissue, GC cell lines (AGS, SUN-1, KATO-III, BGC-823, MGC-803, SGC-7901, and HGC-27), and GES-1 cell line. STAT3 siRNA transfection and genome microarray were applied to demonstrate whether the expression of VEGF-D was mediated by the STAT3 in GC.
We showed the STAT3, pSTAT3, and VEGF-D expression in GC tissue was significantly higher than those in adjacent non-tumor tissue, respectively. In addition, both STAT3 and VEGF-D mRNA expression was much higher in each GC cell line than those in GES-1 cell line. With STAT3 siRNA transfection, we demonstrated that VEGF-D expression level decreased significantly in HGC-27 cell by using the genome microarray representing STAT3 potential regulation the VEGF-D expression.
STAT3, a novel signal transducer inactivating in the GC cell, can contribute to the lymph node metastasis by promoting lymphangiogenesis via up-regulation expression of VEGF-D.
探讨信号转导及转录激活因子3（STAT3）调控血管内皮生长因子D（VEGF-D）促进淋巴管生成的潜在机制。
检测VEGF-D在胃癌组织、癌旁非肿瘤组织、胃癌细胞系（AGS、SUN-1、KATO-III、BGC-823、MGC-803、SGC-7901和HGC-27）及胃黏膜上皮细胞系GES-1中的表达。应用STAT3小干扰RNA转染及基因芯片技术，验证STAT3是否介导胃癌中VEGF-D的表达。
结果显示，胃癌组织中STAT3、磷酸化STAT3及VEGF-D的表达均显著高于癌旁非肿瘤组织。此外，各胃癌细胞系中STAT3及VEGF-D的mRNA表达均明显高于GES-1细胞系。通过STAT3小干扰RNA转染，利用基因芯片技术证实STAT3可能调控VEGF-D的表达，转染后HGC-27细胞中VEGF-D表达水平显著降低。
STAT3作为胃癌细胞中一种新的信号转导因子，可通过上调VEGF-D的表达促进淋巴管生成，进而促进淋巴结转移。
