The Role of Sphingosine-1-phosphate in Breast Cancer Tumor-induced Lymphangiogenesis

Overview

Journal Lymphat Res Biol

Specialty Allergy & Immunology

Date 2012 Sep 19

PMID 22984905

Citations 34

Authors

Tomoyoshi Aoyagi

Masayuki Nagahashi

Akimitsu Yamada

Kazuaki Takabe

Affiliations

Soon will be listed here.

Abstract

Sphingosine-1-phosphate (S1P) is a potent sphingolipid metabolite that regulates a number of biological processes critical for cancer. S1P produced inside cancer cells is exported and exerts its extracellular functions by binding to its specific receptors in an autocrine, paracrine, and/or endocrine manner, which is known as inside-out signaling. S1P is also known to exert its intracellular functions especially in the inflammatory process, but its relevance to cancer biology remains to be elucidated. Recently, there have been growing interests in the role of S1P in breast cancer progression, including angiogenesis and lymphangiogenesis. Our group demonstrated that activation of sphingosine kinase 1, the enzyme that catalyzes the phosphorylation of sphingosine to S1P, is a key step of this process. In this review, we will cover our current knowledge on the role of S1P signaling pathway in breast cancer progression with an emphasis on its role in tumor-induced lymphangiogenesis.

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References

Nagahashi M, Ramachandran S, Rashid O, Takabe K . Lymphangiogenesis: a new player in cancer progression. World J Gastroenterol. 2010; 16(32):4003-12. PMC: 2928453. DOI: 10.3748/wjg.v16.i32.4003. View

Chae S, Paik J, Furneaux H, Hla T . Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J Clin Invest. 2004; 114(8):1082-9. PMC: 522258. DOI: 10.1172/JCI22716. View

Azuma H, Horie S, Muto S, Otsuki Y, Matsumoto K, Morimoto J . Selective cancer cell apoptosis induced by FTY720; evidence for a Bcl-dependent pathway and impairment in ERK activity. Anticancer Res. 2003; 23(4):3183-93. View

Ruckhaberle E, Rody A, Engels K, Gaetje R, von Minckwitz G, Schiffmann S . Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat. 2007; 112(1):41-52. DOI: 10.1007/s10549-007-9836-9. View

Hobson J, Rosenfeldt H, Barak L, Olivera A, Poulton S, Caron M . Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science. 2001; 291(5509):1800-3. DOI: 10.1126/science.1057559. View

Bonnaud S, Niaudet C, Pottier G, Gaugler M, Millour J, Barbet J . Sphingosine-1-phosphate protects proliferating endothelial cells from ceramide-induced apoptosis but not from DNA damage-induced mitotic death. Cancer Res. 2007; 67(4):1803-11. DOI: 10.1158/0008-5472.CAN-06-2802. View

Tedesco-Silva H, Mourad G, Kahan B, Boira J, Weimar W, Mulgaonkar S . FTY720, a novel immunomodulator: efficacy and safety results from the first phase 2A study in de novo renal transplantation. Transplantation. 2005; 79(11):1553-60. View

Xia P, Gamble J, Wang L, Pitson S, Moretti P, Wattenberg B . An oncogenic role of sphingosine kinase. Curr Biol. 2000; 10(23):1527-30. DOI: 10.1016/s0960-9822(00)00834-4. View

Sukocheva O, Wang L, Albanese N, Pitson S, Vadas M, Xia P . Sphingosine kinase transmits estrogen signaling in human breast cancer cells. Mol Endocrinol. 2003; 17(10):2002-12. DOI: 10.1210/me.2003-0119. View

10.

Sugiyama A, Yatomi Y, Ozaki Y, Hashimoto K . Sphingosine 1-phosphate induces sinus tachycardia and coronary vasoconstriction in the canine heart. Cardiovasc Res. 2000; 46(1):119-25. DOI: 10.1016/s0008-6363(00)00013-4. View

11.

Zhang H, Desai N, Olivera A, Seki T, Brooker G, Spiegel S . Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991; 114(1):155-67. PMC: 2289065. DOI: 10.1083/jcb.114.1.155. View

12.

Graler M, Bernhardt G, Lipp M . A lymphoid tissue-specific receptor, EDG6, with potential immune modulatory functions mediated by extracellular lysophospholipids. Curr Top Microbiol Immunol. 1999; 246:131-6; discussion 137. DOI: 10.1007/978-3-642-60162-0_17. View

13.

Ohotski J, Long J, Orange C, Elsberger B, Mallon E, Doughty J . Expression of sphingosine 1-phosphate receptor 4 and sphingosine kinase 1 is associated with outcome in oestrogen receptor-negative breast cancer. Br J Cancer. 2012; 106(8):1453-9. PMC: 3326679. DOI: 10.1038/bjc.2012.98. View

14.

Mulgaonkar S, Tedesco H, Oppenheimer F, Walker R, Kunzendorf U, Russ G . FTY720/cyclosporine regimens in de novo renal transplantation: a 1-year dose-finding study. Am J Transplant. 2006; 6(8):1848-57. DOI: 10.1111/j.1600-6143.2006.01404.x. View

15.

Visentin B, Vekich J, Sibbald B, Cavalli A, Moreno K, Matteo R . Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell. 2006; 9(3):225-38. DOI: 10.1016/j.ccr.2006.02.023. View

16.

Alvarez S, Milstien S, Spiegel S . Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol Metab. 2007; 18(8):300-7. DOI: 10.1016/j.tem.2007.07.005. View

17.

Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E . A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996; 15(2):290-98. PMC: 449944. View

18.

Azuma H, Takahara S, Ichimaru N, Wang J, Itoh Y, Otsuki Y . Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models. Cancer Res. 2002; 62(5):1410-9. View

19.

Watson C, Long J, Orange C, Tannahill C, Mallon E, McGlynn L . High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients. Am J Pathol. 2010; 177(5):2205-15. PMC: 2966780. DOI: 10.2353/ajpath.2010.100220. View

20.

French K, Schrecengost R, Lee B, Zhuang Y, Smith S, Eberly J . Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. 2003; 63(18):5962-9. View