The role of sphingosine-1-phosphate in the tumor microenvironment and its clinical implications
The role of sphingosine-1-phosphate in the tumor microenvironment and its clinical implications
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DOI：
10.1177/1010428317699133
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Masato Nakajima;M. Nagahashi;O. Rashid;K. Takabe;T. Wakai
中科院分区：
文献类型：
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作者：
Masato Nakajima;M. Nagahashi;O. Rashid;K. Takabe;T. Wakai
阐明肿瘤微环境中癌症和非癌细胞（如血管、免疫细胞和其他基质细胞）之间的相互作用对于理解癌症进展和转移的潜在机制至关重要，这有望导致新疗法的开发。鞘氨醇-1-磷酸是一种生物活性脂质介质，可促进细胞存活、增殖、迁移、血管生成/淋巴管生成和免疫反应，这些都是参与癌症进展的因素。鞘氨醇-1-磷酸在癌细胞内由鞘氨醇激酶产生，然后输出到肿瘤微环境中。尽管预计1-磷酸鞘氨醇在肿瘤微环境和癌症进展中发挥重要作用，但由于缺乏既定方法，确定肿瘤微环境中1-磷酸鞘氨醇水平一直很困难。我们最近开发了一种方法来测量在肿瘤微环境中浸润癌细胞的间质液中的鞘氨醇-1-磷酸水平，并报道了高水平的鞘氨醇-1-磷酸存在于肿瘤间质液中。重要的是，鞘氨醇-1-磷酸可以从肿瘤微环境中的癌细胞和非癌组分如免疫细胞和血管/淋巴管内皮细胞分泌。此外，鞘氨醇-1-磷酸影响肿瘤微环境中的癌细胞和非癌细胞，促进癌症进展。本文综述了1-磷酸鞘氨醇在肿瘤微环境中癌细胞与非癌细胞相互作用中的作用，并讨论了针对1-磷酸鞘氨醇信号通路的靶向治疗在癌症患者中的应用前景。
Elucidating the interaction between cancer and non-cancer cells, such as blood vessels, immune cells, and other stromal cells, in the tumor microenvironment is imperative in understanding the mechanisms underlying cancer progression and metastasis, which is expected to lead to the development of new therapeutics. Sphingosine-1-phosphate is a bioactive lipid mediator that promotes cell survival, proliferation, migration, angiogenesis/lymphangiogenesis, and immune responsiveness, which are all factors involved in cancer progression. Sphingosine-1-phosphate is generated inside cancer cells by sphingosine kinases and then exported into the tumor microenvironment. Although sphingosine-1-phosphate is anticipated to play an important role in the tumor microenvironment and cancer progression, determining sphingosine-1-phosphate levels in the tumor microenvironment has been difficult due to a lack of established methods. We have recently developed a method to measure sphingosine-1-phosphate levels in the interstitial fluid that bathes cancer cells in the tumor microenvironment, and reported that high levels of sphingosine-1-phosphate exist in the tumor interstitial fluid. Importantly, sphingosine-1-phosphate can be secreted from cancer cells and non-cancer components such as immune cells and vascular/lymphatic endothelial cells in the tumor microenvironment. Furthermore, sphingosine-1-phosphate affects both cancer and non-cancer cells in the tumor microenvironment promoting cancer progression. Here, we review the roles of sphingosine-1-phosphate in the interaction between cancer and non-cancer cells in tumor microenvironment, and discuss future possibilities for targeted therapies against sphingosine-1-phosphate signaling for cancer patients.