Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis.
Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis.
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DOI：
10.1038/s41598-021-85162-0
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发表时间：
2021-03-11
影响因子：
4.6
通讯作者：
László V
中科院分区：
文献类型：
--
作者：
Berta J;Török S;Tárnoki-Zách J;Drozdovszky O;Tóvári J;Paku S;Kovács I;Czirók A;Masri B;Megyesfalvi Z;Oskolás H;Malm J;Ingvar C;Markó-Varga G;Döme B;László V
Apelin是APJ受体的一种配体，在多种人类癌症中过表达，在各种实验系统中对肿瘤血管生成和生长起重要作用。我们研究了apelin信号在皮肤黑色素瘤恶性行为中的作用。用apelin编码载体或对照载体稳定转染小鼠B16和人A375黑色素瘤细胞系。Apelin过表达显著增加黑色素瘤细胞在体外的迁移和侵袭，但对其增殖无影响。在我们的体内实验中，apelin显著增加了小鼠黑色素瘤细胞肺转移的数量和大小。过表达apelin的肺转移瘤的黑色素瘤细胞增殖率、淋巴和血管微血管密度显著增高。竞争性APJ拮抗剂MM54对APJ的抑制作用显著减弱了APJ在体内的促肿瘤作用。此外，与健康对照相比，我们检测到黑色素瘤患者的循环apelin和VEGF水平显著升高。我们的研究结果表明，apelin促进血液和淋巴血管的形成以及皮肤黑色素瘤肺转移瘤的生长。需要进一步的研究来验证apelin信号作为一种新的潜在治疗靶点。
Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
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DOI：
10.1093/brain/awx253
发表时间：
2017-11-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Harford-Wright E;Andre-Gregoire G;Jacobs KA;Treps L;Le Gonidec S;Leclair HM;Gonzalez-Diest S;Roux Q;Guillonneau F;Loussouarn D;Oliver L;Vallette FM;Foufelle F;Valet P;Davenport AP;Glen RC;Bidere N;Gavard J
通讯作者：
Gavard J
影响因子：
3.8
作者：
Feng M;Yao G;Yu H;Qing Y;Wang K
通讯作者：
Wang K
影响因子：
3.7
作者：
Gulyas M;Csiszer M;Mehes E;Czirok A
通讯作者：
Czirok A
影响因子：
0.7
作者：
De Wever, Olivier;Hendrix, An;Bracke, Marc
通讯作者：
Bracke, Marc
影响因子：
4.6
作者：
Czirok A;Isai DG;Kosa E;Rajasingh S;Kinsey W;Neufeld Z;Rajasingh J
通讯作者：
Rajasingh J