Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis
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Lan Dai1,2,*, Yixuan Liu1,2,*, Lei Xie1,2,*, Xia Wu1,2, Lihua Qiu1,2,3 and Wen Di1,2,3
1Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
2Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
3State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
*These authors have contributed equally to this work
Wen Di, email: [email protected]
Lan Dai, email: [email protected]
Keywords: sphingosine kinase 1 (SphK1), sphingosine-1-phosphate (S1P), S1P receptor (S1PR), angiogenesis, ovarian cancer
Received: March 28, 2017 Accepted: July 25, 2017 Published: August 24, 2017
Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro, the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR1 and S1PR3, but not S1PR2. Furthermore, inhibition of S1PR1/3, but not S1PR2, attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo, blockage of SphK or S1PR1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.
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