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Invasionsmechanismen und Metastasierung des Urothelkarzinoms

Eine Herausforderung für die translationale Forschung

Invasion patterns and metastasis of urothelial carcinoma

A challenge for translational research

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Zusammenfassung

Die Invasion von Tumorzellen tritt früh im Rahmen der lokalen Tumorprogression aggressiver Urothelkarzinome auf. Eine Mikrometastasierung in Lymph- oder Blutgefäße sowie das Vorhandensein von Lymphknotenmetastasen sind wichtige Prognosefaktoren für die krankheitsspezifische Mortalität. Der Metastasierungsprozess ist komplex und umfasst eine Kaskade multipler aufeinanderfolgender Schritte.

Für das Urothelkarzinom existieren wenige Daten aus präklinischen Studien über diese Mechanismen. Verschiedene Proteasen, Chemokine und Wachstumsfaktoren sind am Metastasierungsprozess beteiligt und pathophysiologische Veränderungen des Lymphgefäßsystems begünstigen die systemische Aussaat von Tumorzellen. Es besteht ein hoher Bedarf, neue Therapiemöglichkeiten zu entwickeln mit dem Ziel, in den Metastasierungsprozess einzugreifen.

Wir fassen Erkenntnisse über die Invasion und Metastasierung des Urothelkarzinoms zusammen und präsentieren ein innovatives experimentelles Modell, das funktionelle Aspekte berücksichtigt und dazu beitragen kann, die Mechanismen der Invasion besser zu verstehen sowie neue therapeutische Zielstrukturen zu identifizieren.

Abstract

Local invasion of cancer cells occurs early during the progression of urothelial carcinoma. Micrometastatic disease and the presence of nodal metastases are major causes of cancer-specific mortality following radical surgery. Only surrogate markers for aggressive and micrometastatic disease have been identified. The metastatic cascade is complex, including multiple steps from initial invasion to colonization and proliferation at distant sites.

The initial mechanisms of cancer cell dissemination in urothelial carcinoma are poorly understood. Various proteases, chemokines and growth factors are involved in this process and alterations of the lymphatic system may promote systemic spread. There is a high demand for therapeutic targeting of the metastatic process. Functional preclinical studies in representative models are therefore required to better elucidate the multiple steps of progression.

We review the current knowledge on factors associated with metastasis in urothelial carcinoma. Preclinical approaches to identify key player molecules for invasion and to develop new therapeutic strategies are discussed.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. C. Bolenz, T. Martini und M.S. Michel geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik für Urologie, Universitätsmedizin Mannheim, Fakultät für Medizin der Universität Heidelberg, Theodor-Kutzer-Ufer 1, 68167, Mannheim, Deutschland

    C. Bolenz, T. Martini & M.S. Michel

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  1. C. Bolenz
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  2. T. Martini
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  3. M.S. Michel
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Correspondence to C. Bolenz.

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Bolenz, C., Martini, T. & Michel, M. Invasionsmechanismen und Metastasierung des Urothelkarzinoms. Urologe 52, 1242–1247 (2013). https://doi.org/10.1007/s00120-013-3309-z

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