Apelin promotes lymphangiogenesis and lymph node metastasis.
Apelin promotes lymphangiogenesis and lymph node metastasis.
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DOI：
10.18632/oncotarget.2032
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发表时间：
2014-06-30
期刊：
影响因子：
--
通讯作者：
Dome B
中科院分区：
文献类型：
--
作者：
Berta J;Hoda MA;Laszlo V;Rozsas A;Garay T;Torok S;Grusch M;Berger W;Paku S;Renyi-Vamos F;Masri B;Tovari J;Groger M;Klepetko W;Hegedus B;Dome B
尽管G蛋白偶联的APJ受体及其配体爱帕琳在血管生成中的作用已被充分证明，但爱帕琳/APJ系统诱导淋巴管生成和淋巴转移的能力在很大程度上尚未被探索。为此，我们首先表明，APJ表达在淋巴管内皮细胞（LEC），而且，它响应爱帕琳激活爱帕琳能信号级联。我们发现，虽然爱帕琳肽治疗不影响体外淋巴管内皮细胞的增殖，但它增强了它们的迁移，保护它们免受紫外线照射诱导的凋亡，增加了它们在3D培养中的球状体数量，刺激它们在体外毛细血管样管的形成，此外，在基质胶塞测定中促进了体内淋巴管微血管的侵入性生长。我们还证明，爱帕琳蛋白在恶性细胞中的过度表达与体内肿瘤生长加速以及肿瘤内淋巴管生成和淋巴结转移增加相关。这些结果表明，爱帕琳诱导淋巴管生成，因此，在淋巴肿瘤进展中起重要作用。我们的研究不仅揭示了爱帕琳作为一种新的淋巴管生成因子，而且还可能为开发以淋巴管生成为靶点的新型抗癌疗法打开大门。
Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated in vivo tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis.
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DOI：
10.1161/atvbaha.113.302785
发表时间：
2014-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Kim JD;Kang Y;Kim J;Papangeli I;Kang H;Wu J;Park H;Nadelmann E;Rockson SG;Chun HJ;Jin SW
通讯作者：
Jin SW
影响因子：
4.8
作者：
Masri, B;Morin, N;Audigier, Y
通讯作者：
Audigier, Y
影响因子：
3.7
作者：
Bai, Bo;Tang, Jiyou;Song, Wengang
通讯作者：
Song, Wengang
Apelin 通过 APJ/PI3-K/Akt 信号通路抑制人血管平滑肌细胞凋亡
影响因子：
3.5
作者：
Cui, Rong-Rong;Mao, Ding-An;Liao, Er-Yuan
通讯作者：
Liao, Er-Yuan
影响因子：
--
作者：
Duong T;Koopman P;Francois M
通讯作者：
Francois M