PEDF inhibits lymphatic metastasis of nasopharyngeal carcinoma as a new lymphangiogenesis inhibitor.
PEDF inhibits lymphatic metastasis of nasopharyngeal carcinoma as a new lymphangiogenesis inhibitor.
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PEDF作为新型淋巴管生成抑制剂抑制鼻咽癌淋巴转移
DOI：
10.1038/s41419-021-03583-1
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发表时间：
2021-03-17
影响因子：
9
通讯作者：
Zhou T
中科院分区：
文献类型：
--
作者：
Luo C;Yin H;Gao T;Ma C;Liu J;Zhang T;Xu Z;Wang X;Zhang D;Qi W;Yang Z;Gao G;Yang X;Zhou T
鼻咽癌是我国南方乃至亚洲地区最常见的恶性肿瘤之一，淋巴结转移是导致治疗失败的重要原因。淋巴管生成是鼻咽癌淋巴道转移的重要环节，但目前对鼻咽癌淋巴管生成的研究还不多。与血管生成相似，淋巴管炎性新生血管是促淋巴管生成因子和抗淋巴管生成因子之间的平衡过程，但对内源性淋巴管生成抑制因子的研究较少。色素上皮衍生因子（PEDF）是一种有效的内源性血管生成抑制因子。然而，PEDF和淋巴管生成之间的关系仍然未知。我们的研究表明PEDF在人鼻咽癌组织中低表达，且与淋巴管密度（LVD）呈负相关。因此，PEDF在体内实验中抑制NPC淋巴管生成和淋巴道转移。从机制上讲，PEDF抑制淋巴管内皮细胞的增殖、迁移和管形成，并促进细胞凋亡。另一方面，PEDF通过核因子-κB（NF-κB）信号通路降低鼻咽癌细胞血管内皮生长因子C（VEGF-C）的表达和分泌。我们的研究结果表明，PEDF通过靶向淋巴管内皮细胞和NPC细胞在淋巴转移中起着至关重要的作用，PEDF可能代表NPC的新的治疗靶点。
Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in southern China and Asia, and lymph node metastasis is an important cause for treatment failure. Lymphangiogenesis is a crucial step in lymphatic metastasis of NPC, while little is known about lymphangiogenesis in NPC. Similar to angiogenesis, lymphangitic neovascularization is a process of balance between pro-lymphangiogenesis and anti-lymphangiogenesis factors, but there are few studies on endogenous lymphangiogenesis inhibitors. Pigment epithelium-derived factor (PEDF) is a well-known effective endogenous angiogenesis inhibitor. However, the relationship between PEDF and lymphangiogenesis remains unknown. Our present study reveals that PEDF is lowly expressed in human NPC tissues with poor prognosis and is negatively correlated with lymphatic vessel density (LVD). Consistently, PEDF inhibits lymphangiogenesis and lymphatic metastasis of NPC in vivo experiments. Mechanistically, PEDF inhibits the proliferation, migration, and tube formation of lymphatic endothelial cells and promotes cell apoptosis. On the other hand, PEDF reduces the expression and secretion of vascular endothelial growth factor C (VEGF-C) of NPC cells through the nuclear factor-κB (NF-κB) signaling pathway. Our findings indicate that PEDF plays a vital role in lymphatic metastasis by targeting both lymphatic endothelial cells and NPC cells, and PEDF may represent a novel therapeutic target for NPC.
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