Karnezis Tara, Shayan Ramin, Fox Stephen, Achen Marc G, Stacker Steven A
Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, East Melbourne, Victoria, Australia.
Oncotarget. 2012 Aug;3(8):893-906. doi: 10.18632/oncotarget.593. Epub 2012 Aug 19.
Substantial evidence supports important independent roles for lymphangiogenic growth factor signaling and prostaglandins in the metastatic spread of cancer. The significance of the lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C and VEGF-D, is well established in animal models of metastasis, and a strong correlation exits between an increase in expression of VEGF-C and VEGF-D, and metastatic spread in various solid human cancers. Similarly, key enzymes that control the production of prostaglandins, cyclooxygenases (COX-1 and COX-2, prototypic targets of Non-steroidal anti-inflammatory drugs (NSAIDs)), are frequently over-expressed or de-regulated in the progression of cancer. Recent data have suggested an intersection of lymphangiogenic growth factor signaling and the prostaglandin pathways in the control of metastatic spread via the lymphatic vasculature. Furthermore, this correlates with current clinical data showing that some NSAIDs enhance the survival of cancer patients through reducing metastasis. Here, we discuss the potential biochemical and cellular basis for such anti-cancer effects of NSAIDs through the prostaglandin and VEGF signaling pathways.
大量证据支持淋巴管生成生长因子信号传导和前列腺素在癌症转移扩散中发挥重要的独立作用。淋巴管生成生长因子血管内皮生长因子（VEGF）-C和VEGF-D在转移动物模型中的重要性已得到充分证实，并且在多种实体人类癌症中，VEGF-C和VEGF-D表达的增加与转移扩散之间存在密切关联。同样，控制前列腺素生成的关键酶环氧化酶（COX-1和COX-2，非甾体抗炎药（NSAIDs）的典型靶点）在癌症进展过程中经常过度表达或失调。最近的数据表明，淋巴管生成生长因子信号传导与前列腺素途径在通过淋巴管系统控制转移扩散方面存在交集。此外，这与当前临床数据相关，该数据表明一些NSAIDs通过减少转移来提高癌症患者的生存率。在此，我们讨论NSAIDs通过前列腺素和VEGF信号通路产生此类抗癌作用的潜在生化和细胞基础。
