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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Korrespondenzadresse
Prof. Dr. rer. nat. Thomas Dittmar
Institut für Immunologie
Universität
Witten/Herdecke
Stockumer Str. 10
58448 Witten
eMail: thomas.dittmar@uni-wh.de
