Zusammenfassung
Sämtliche Stufen der Metastasierung (Invasion von Basalmembranen und Bindegewebe, Intra- und Extravasation, Absiedelung am Metastasenort) erfordern Kontakte von Tumorzellen zu anderen Zellen (z. B. Endothelzellen) und zu Molekülen der extrazellulären Matrix (z. B. Basalmembrankomponenten). Das Migrationsverhalten invasiv wachsender Tumorzellen, möglicherweise auch die Aktivierung matrixdegradierender Enzymsysteme wird hierbei z. T. durch Signalvermittlungen über Zelloberflächenrezeptoren für Zell-Zell- und Zell-Matrix-Adhäsionen reguliert. Zu diesen Rezeptoren zählen Moleküle verschiedener Genfamilien, von denen die Rolle der sog. Integrine mit ihren einzelnen Subfamilien (VLA-Proteine, Cytoadhäsine, Leukozytenintegrine) als Hauptvertreter für Zell-Matrixkontakte und für Zell-Zell-Interaktionen im Rahmen der Tumorprogression wachsende Bedeutung gewinnt. Auch der Organotropismus von Metastasen bestimmter Primärtumoren kann teilweise durch eine selektiv bevorzugte Adhäsion von metastatischen Tumorzellen an Endothelien der Zielorgane als Voraussetzung für eine dortige Extravasation erklärt werden. Die Entschlüsselung der Interaktionen zwischen adhäsiven Zell-Zell- und Zell-Matrix-Interaktionen und den dabei involvierten Rezeptor-Liganden-Beziehungen ermöglicht somit nicht nur Einblicke in Regulationsvorgänge der Tumorinvasion auf molekularer Ebene, sondern erweitert auch das Verständnis um das Metastasierungsmuster und metastatische Potential bestimmter Malignome. Zukünftig könnten solche Erkenntnisse Bedeutung gewinnen für die Prognoseabschätzung maligner Primärtumoren, aber auch die Basis für neue therapeutische Ansatzpunkte (Adhäsionsblockade) eröffnen.
Summary
Each single step of the metastatic cascade (invasion of basement membranes and connective tissue, intra- und extravasation, formation of metastatic colonies) requires the establishment of contacts between tumor cells and other cells (e.g., endothelial cells) or extracellular matrix molecules (e.g., components of basement membranes). The migration of invading tumor cells, possibly also the activation of matrix-degrading enzyme systems, is thought to be regulated by adhesion-mediated signal transduction involving cell surface receptors for both cell-cell and cell- matrix adhesion. These adhesion receptors include different gene families, among which the integrins and their subgroups (VLA proteins, cytoadhesins, leukocyte integrins) seem to play a major role in tumor progression. Moreover, the organotropism of metastases originating from certain malignancies is believed to depend in part on a selective adhesion advantage of tumor cells in target tissues. The exploration of receptors and ligands involved in adhesive cell-cell and cell- matrix interactions thus permits insights into the regulation of tumor cell invasion on a molecular level and moreover will enhance our understanding about the metastatic behavior and potential of particular malignancies. Such knowledge could be of clinical value in the assessment of tumor prognosis and also provides a base for the development of innovative therapeutic approaches (adhesion blocking).
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Kaufmann, R. (1992). Adhäsionsmoleküle und Metastasierungsverhalten. In: Burg, G., Hartmann, A.A., Konz, B. (eds) Onkologische Dermatologie. Fortschritte der operativen und onkologischen Dermatologie, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77690-8_4
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