Chronische Entzündungen – Rolle am Tumorgeschehen

Zusammenfassung

Die Erkenntnis, dass ein Zusammenhang zwischen chronischen Entzündungen und einem erhöhten Krebsrisiko besteht, wurde bereits vor mehr als 150 Jahren vom Berliner Mediziner Rudolph Virchow beschrieben. Heute wird vermutet, dass ca. 10-15 % aller humanen Krebserkrankungen auf chronische Entzündungsprozesse zurückzuführen sind, wobei die Ursachen sowohl auf humanpathogene Keime (z. B. Helicobacter pylori) als auch auf anorganische/organische Substanzen/Faktoren (Asbestfasern, Magensäure, Zigarettenrauch) zurückgeführt werden können. Chronisch entzündetes Gewebe stellt ein potenziell transformierendes Milieu dar, da es reich an Wachstumsfaktoren, Zytokinen und Chemokinen ist, welche die proliferatorische Aktivität von Zielzellen triggern, sowie an radikalischen Sauerstoff-/Stickstoffverbindungen, die bei hoher Konzentration Schädigungen der DNS bewirken. Durch die Faktor vermittelte bzw. inhärente Zellteilungsaktivität der Zielzellen, kombiniert mit mutagen wirkenden radikalischen Sauerstoff-/Stickstoffverbindungen, kann es zur Akkumulation von chromosomalen Aberrationen und nachfolgend zur malignen Transformation der Zielzellen kommen. Entgegen der alten Lehrmeinung, dass Krebs seinen Ursprung in somatischen Zellen hat, ist heute bekannt, dass die Ursprungszellen für maligne Transformationen Stammzellen (Gewebestammzellen bzw. rekrutierte Knochenmarkstammzellen) bzw. deren Progenitorzellen sind, aus denen die tumorinitiierenden Krebsstammzellen hervorgehen. So konnte z. B. anhand eines etablierten Mausmodells zur Analyse des durch H. felis induzierten Magenadenokarzinoms gezeigt werden, dass das neoplastische Gewebe aus rekrutierten Knochenmarkstammzellen hervorgegangen ist. Neben ihrer Rolle in der Karzinogenese sind chronische Entzündungsreaktionen darüber hinaus maßgeblich an der Progression von Tumorerkrankungen beteiligt. Fatal hierbei ist die symbiotische Beziehung zwischen tumorassoziierten Makrophagen (TAM) und Tumorzellen. TAM sind an sämtlichen Prozessen beteiligt, die eine erhöhte Malignität der Tumorerkrankung nach sich ziehen. Hierzu zählen die Neoangiogenese, die Proliferation sowie die Invasion und Metastasierung von Tumorzellen wie auch die Suppression von zytotoxischen T-Zellen.

Summary

The connection between chronically inflamed tissues and an increased risk to get cancer was already described by Rudolph Virchow nearly 150 years ago. Today, we know that about 10 to 15 % of human cancers are attributed to chronic infections and/or inflammatory conditions caused by pathogens like Helicobacter pylori and/or inorganic/organic agents such as asbestos fibers, gastric acid or smoke. Chronically inflamed tissues are characterized by an aberrant mix of growth factors, cytokines and chemokines, which induce cell proliferation, as well as reactive oxygen and nitrogen species that will cause DNA damages. Thus, chronically inflamed tissues exhibit an increased cell transformation capacity because dividing cells could accumulate chromosomal aberrations, which ultimately can give rise to a malignant phenotype. To date, we know that cancer has its origin in cancer stem cells, which can originate from either adult tissue stem cells or committed progenitor cells. In case of chronically inflamed gastric tissue it was demonstrated that gastric cancer can originate from recruited bone marrow-derived stem cells. Chronically inflamed conditions do also play a role in tumor progression since tumor tissue resembles chronically inflamed tissues. Thereby, a pivotal role has been addressed to tumor-associated macrophages (TAMs). TAMs are stimulated by tumor cells and vice versa thus indicating a symbiotically relationship between these cellular entities. In fact, TAMs are participated in all mechanisms that increase tumor malignancy including neoangiogenesis, proliferation, invasion and metastasis as well as suppression of cytotoxic T lymphocytes.

Schlüsselwörter

Chronische Entzündungen - Chronische Infektionen - Tumorgenese

Keywords

chronic inflammation - chronic infection - tumorgenesis - cancer stem cells

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