Metastasis-associated in colon cancer-1 upregulates vascular endothelial growth factor-C/D to promote lymphangiogenesis in human gastric cancer
Metastasis-associated in colon cancer-1 upregulates vascular endothelial growth factor-C/D to promote lymphangiogenesis in human gastric cancer
复制标题
结肠癌转移相关-1上调血管内皮生长因子-C/D以促进人胃癌淋巴管生成
DOI：
10.1016/j.canlet.2014.11.035
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发表时间：
2015-02-01
期刊：
影响因子：
9.7
通讯作者：
Liao, Wangjun
中科院分区：
文献类型：
--
作者：
Sun, Li;Duan, Jiangman;Liao, Wangjun
淋巴管生成是胃癌淋巴道转移的重要因素，血管内皮生长因子（VEGF）-C和VEGF-D是淋巴管生成的关键调节因子。结肠癌转移相关基因1（MACC 1）与淋巴结转移相关，但MACC 1在淋巴管生成中的作用尚不清楚。因此，在本研究中，我们探讨了MACC 1在淋巴管生成中的潜在作用以及潜在机制。通过临床观察，我们发现MACC 1与淋巴管生成呈正相关。此外，体内和体外研究也获得了类似的结果。通过间接共培养体系，我们发现MACC 1过表达的GC细胞培养上清通过促进细胞增殖和迁移，促进人淋巴管内皮细胞（human lymphocyte endothelial cells，HLEC）的管状形成能力。此外，MACC 1过表达的异种移植物也呈现出更多的淋巴管。此外，MACCI还能显著增加胃癌细胞和移植瘤中VEGF-C/VEGF-D的表达，而c-Met抑制剂则能抑制这种表达。所有这些数据表明MACC 1在GC的淋巴播散中起关键作用，提供了MACC 1上调VEGF-C/VEGF-D分泌以通过c-Met信号传导促进淋巴管生成的证据。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Lymphangiogenesis is actively contributed to lymphatic metastasis in gastric cancer (GC), and vascular endothelial growth factor (VEGF)-C and VEGF-D are key regulators for lymphangiogenesis. Metastasis-associated in colon cancer-1 (MACC1) was reported to be associated with lymph node metastasis in a few clinical studies, while little is known about the role of MACC1 in lymphangiogenesis. Hence, in the present study, we explored the potential role of MACC1 in lymphangiogenesis as well as the underlying mechanisms. By clinical observation, we found a positive relationship between MACC1 and lymphangiogenesis. Besides, similar results were also obtained from in vivo and in vitro studies. With an indirect co-culture system, we got that supernatant from MACC1 overexpressed GC cells accelerated human lymphatic endothelial cells' (HLECs') capacity of tube-like formation through enhancing cell proliferation and migration. Moreover, MACC1 overexpressed xenografts also presented more lymphatic vessels. Furthermore, MACCI significantly increased the expression of VEGF-C/VEGF-D in GC cells and transplanted tumors, which was subsequently suppressed by c-Met inhibitor. All these data suggested a critical role for MACC1 in lymphatic dissemination of GC, providing evidence that MACC1 upregulated VEGF-C/VEGF-D secretion to promote lymphangiogenesis via c-Met signaling. (C) 2014 Elsevier Ireland Ltd. All rights reserved.