Subscribe to RSS
DOI: 10.1055/s-0029-1186175
© Georg Thieme Verlag KG Stuttgart · New York
Does Sphingosine Kinase 1 (SPHK1) Play a Role in Endometriosis?
Spielt Sphingosinkinase 1 (SPHK1) eine potenzielle Rolle bei Endometriose?Publication History
received 1.9.2009
revised 2.9.2009
accepted 4.9.2009
Publication Date:
22 October 2009 (online)
![](https://www.thieme-connect.de/media/gebfra/200910/lookinside/thumbnails/10.1055-s-0029-1186175-1.jpg)
Abstract
Sphingolipids are important constituents of cell membranes, which play key roles as regulatory molecules for various cellular functions. Sphingosine-1-phosphate produced by sphingosine kinase 1 (SPHK1) promotes cell proliferation, regulates angiogenesis, and influences invasion as well as the attachment of cells. Since these processes are believed to be involved in the development of endometriosis, we analyzed the expression of SPHK1 in human eutopic and ectopic endometrium using immunohistochemistry and microarray analysis. Epithelial cells of both eutopic and ectopic endometrium showed highly variable immunostaining with polyclonal antibody directed against SPHK1. However, strong expression of SPHK1 was largely restricted to the epithelial endometrial cells of peritoneal endometriotic lesions (n = 8/23, 34.8 %). Only n = 1/15 (6.7 %) of the adenomyosis samples and n = 3/41 (7.3 %) of the eutopic endometrium samples displayed strong antigen expression (p = 0.008, χ2 test). No association between SPHK1 and Ki-67 expression was detectable. Still further research is needed in order to clarify the role of sphingolipids in the development of endometriosis, and particularly in invasive growth.
Zusammenfassung
Sphingolipide sind wichtige Bestandteile der Zellmembran, die eine Schlüsselrolle in der Regulation verschiedener Zellfunktionen haben. Sphingosine-1-Phosphat, das durch Sphingosinkinnase 1 (SPHK1) entsteht, fördert die Zellproliferation, reguliert die Angiogenese und beeinflusst sowohl die Invasivität als auch die Adhäsion von Zellen. Da diese Prozesse in der Entwicklung der Endometriose bekanntermaßen eine wichtige Rolle haben, wurde die Expression von SPHK1 im eutopen und ektopen humanen Endometrium durch Immunhistochemie und Mikroarray-Analysen untersucht. Die Epithelzellen von Endometrioseherden des Peritoneums zeigen häufiger eine starke Expression von SPHK1 verglichen mit denen des eutopen Endometriums oder der Adenomyosis uteri (p = 0,008, χ2-Test). Eine Assoziation zwischen SPHK1 und Ki67-Epxression konnte nicht gefunden werden. Diese ersten Ergebnisse sollten Anlass für weitere Untersuchungen zur Rolle der Sphingolipide in der Entwicklung der Endometriose, insbesondere des invasiven Wachstumspotenzials, sein.
Key words
adenomyosis - endometrium - S1P - sphingolipids - peritoneum
Schlüsselwörter
Adenomyosis - Endometrium S1P - Sphingolipide - Peritoneum
References
- 1 Ogretmen B, Hannun Y A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer. 2004; 4 604-616
- 2 Hannun Y A, Obeid L M. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008; 9 139-150
- 3 Alemany R, van Koppen C J, Danneberg K et al. Regulation and functional roles of sphingosine kinases. Naunyn-Schmiedeberg's Arch Pharmacol. 2007; 374 413-428
- 4 Kawamori T, Kaneshiro T, Okumura M et al. Role for sphingosine kinase 1 in colon carcinomgenesis. FASEB J. 2009; 23 405-414
- 5 Cuvillier O. Sphingosine kinase-1 – a potential therapeutic target in cancer. Anticancer Drugs. 2007; 18 105-110
- 6 Smicun Y, Gil O, Devine K et al. SIP and LPA have an attachment-dependent regulatory effect on invasion of epithelial ovarian cancer cells. Gynaecol Oncol. 2007; 107 298-309
- 7 Ruckhäberle E, Rody A, Engels K et al. Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat. 2008; 112 41-52
- 8 Gaetje R, Kotzian S, Herrmann G et al. Invasiveness of endometriotic cells in vitro. Lancet. 1995; 346 1463-1464
- 9 Gaetje R, Holtrich U, Engels K et al. Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract. Fertil Steril. 2007; 87 651-656
- 10 Gaetje R, Holtrich U, Karn T et al. Characterization of WNT7A expression in human endometrium and endometriotic lesions. Fertil Steril. 2007; 88 1534-1540
- 11 Gaetje R, Holtrich U, Engels K et al. Differential expression of claudins in human endometrium and endometriosis. Gynecol Endocrinol. 2008; 24 442-449
- 12 Gaetje R, Holtrich U, Engels K et al. Expression of membrane-type 5 matrix metalloproteinase in human endometrium and endometriosis. Gynecol Endocrinol. 2007; 23 567-573
- 13 Burney R O, Talbi S, Hamilton A E et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007; 148 3814-3826
- 14 Bulun S E. Endometriosis. N Engl J Med. 2009; 360 268-279
- 15 Olivares C, Bilotas M, Buquet R et al. Effects of a selective cycloxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Hm Reprod. 2008; 23 2701-2708
- 16 Dogan E, Saygili U, Posaci C et al. Regression of endometrial explants in rats treated with cyclooxygenase-2 inhibitor rofecoxib. Fertil Steril. 2004; 82 1115-1120
- 17 Ozawa Y, Murakami T, Tamura M et al. A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice. Fertil Steril. 2006; 86 1146-1151
Prof. Dr. med. Regine Gaetje
Department of Obstetrics and Gynecology
Johann Wolfgang Goethe University
Theodor-Stern-Kai 7
60596 Frankfurt
Email: gaetje@em.uni-frankfurt.de