Epithelial-zu-mesenchymale Transition (EMT) – Neue molekulare Einsichten in die Tumorprogression

Zusammenfassung

Die maligne Progression gynäkologischer Tumoren wird wesentlich durch ihr Invasions- und Metastasierungsverhalten bestimmt. Es bedarf verschiedener Veränderungen auf molekularer und zellulärer Ebene, damit sich Krebszellen aus dem epithelialen Zellverband lösen und in die Umgebung invadieren bzw. metastasieren können. Für beide Prozesse müssen Tumorzellen die Fähigkeit erwerben, von einem epithelialen in einen mesenchymalen Zustand überzugehen, einen Vorgang, den man als epithelial-zu-mesenchymale Transition (EMT) bezeichnet. In dieser Arbeit beschreiben wir die Bedeutung der EMT für gynäkologische Karzinome anhand aktueller Forschungsergebnisse. In den hier betrachteten Malignomen – Mamma-, Ovarial- und Zervixkarzinom – wurde eine Vielzahl von EMT-typischen Veränderungen beschrieben. Dabei waren der Verlust epithelialer Marker (E-Cadherin, Zytokeratine) und die Zunahme mesenchymaler Marker (z. B. N-Cadherin, Vimentin) charakteristisch. Auch Transkriptionsfaktoren der EMT wie Snail und Twist wurden in verschiedenen Tumorentitäten nachgewiesen. Als wesentliche Stimuli der EMT gelten Wachstumsfaktoren (z. B. TGF-β), WNT- und Notch-Signaling sowie Tumorhypoxie. Typische EMT-Veränderungen lassen sich in gynäkologischen Malignomen nachweisen und man muss davon ausgehen, dass auch in diesen Karzinomen Invasions- und Metastasierungsvorgänge – und damit die maligne Progression – durch EMT getriggert werden. Aus der genauen Analyse der EMT lassen sich neue molekulare Targets für eine gezielte Tumortherapie identifizieren.

Abstract

The malignant progression of gynecologic tumors is determined by their potential for invasion and metastasis. Specifically, epithelial tumor cells need to leave the primary tumor mass to invade the environment and/or metastasize to distant regions. To do so, these tumor cells undergo distinct changes from an epithelial to a mesenchymal phenotype, a process called epithelial-to-mesenchymal transition (EMT). In this article, we review the significance of EMT-related mechanisms in gynecologic malignancies. For the cancers considered here – breast, ovarian and cervical carcinomas – a multitude of EMT events have been described, including the loss of epithelial markers (E-cadherin, cytokeratines) and an increase in mesenchymal markers (e.g. N-cadherin, vimentin). In addition, the expression of the EMT transcription factors Snail and Twist has been observed in different malignancies. EMT can be induced by several stimuli, e.g. growth factors, WNT and notch signaling as well as tumor hypoxia, a common feature of solid tumors. Characteristic EMT-related changes can be detected in gynecologic cancers, suggesting a role for EMT in triggering invasion, metastasis and, therefore, malignant progression in these tumor entities. Further investigation of EMT pathways will result in the identification of new targets for tailored cancer therapies.

epithelial‐zu‐mesenchymale Transition - Hypoxie - Mammakarzinom - Zervixkarzinom - Ovarialkarzinom

epithelial‐to‐mesenchymal transition - hypoxia - breast cancer - cervical cancer - ovarian cancer

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