Does Sphingosine Kinase 1 (SPHK1) Play a Role in Endometriosis?

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

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