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Plasma Sphingosine-1-Phosphate Levels Are Associated with Progression of Estrogen Receptor-Positive Breast Cancer
Authors:Mayuko Ikarashi  Junko Tsuchida  Masayuki Nagahashi  Shiho Takeuchi  Kazuki Moro  Chie Toshikawa  Shun Abe  Hiroshi Ichikawa  Yoshifumi Shimada  Jun Sakata  Yu Koyama  Nobuaki Sato  Nitai C Hait  Yiwei Ling  Shujiro Okuda  Kazuaki Takabe  Toshifumi Wakai
Abstract:Although numerous experiments revealed an essential role of a lipid mediator, sphingosine-1-phosphate (S1P), in breast cancer (BC) progression, the clinical significance of S1P remains unclear due to the difficulty of measuring lipids in patients. The aim of this study was to determine the plasma concentration of S1P in estrogen receptor (ER)-positive BC patients, as well as to investigate its clinical significance. We further explored the possibility of a treatment strategy targeting S1P in ER-positive BC patients by examining the effect of FTY720, a functional antagonist of S1P receptors, on hormone therapy-resistant cells. Plasma S1P levels were significantly higher in patients negative for progesterone receptor (PgR) expression than in those positive for expression (p = 0.003). Plasma S1P levels were also significantly higher in patients with larger tumor size (p = 0.012), lymph node metastasis (p = 0.014), and advanced cancer stage (p = 0.003), suggesting that higher levels of plasma S1P are associated with cancer progression. FTY720 suppressed the viability of not only wildtype MCF-7 cells, but also hormone therapy-resistant MCF-7 cells. Targeting S1P signaling in ER-positive BC appears to be a possible new treatment strategy, even for hormone therapy-resistant patients.
Keywords:sphingosine-1-phosphate  breast cancer  lymph node metastasis  plasma  mass spectrometry  estrogen receptor  progesterone receptor  hormone therapy
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