Zusammenfassung
Mit den Erkenntnissen der letzten Jahre, wird es immer offensichtlicher, dass Stammzellen
eine zentrale Rolle in der Re- und Generation von Geweben einnehmen. Besonders deutlich
lässt sich dies an der Entwicklung von Karzinomen zeigen. Primär werden 2 Arten von
Stammzellfunktionen unterschieden, beide Stammzellarten sind von entscheidender Bedeutung
für die Initiierung und Aufrechterhaltung eines Tumors. Zum einen werden Tumore von
einer Vielzahl von Stammzellen infiltriert, die vom Tumor für verschiedene Funktionen
genutzt werden, z. B. für den Aufbau von Gefäßen aber auch anderen Gewebeanteilen.
Dennoch sind diese Stammzellen per se nicht maligne. Andererseits lassen sich auch
die tumorinitiierenden Tumorstammzellen (CSC) nachweisen. Sie sind in der Lage aus
jeder einzelnen Zelle einen Tumor entstehen zu lassen, der histologisch dem gleicht,
aus dem die originale CSC entstammt. Vieles ist an der CSC- Biologie nicht verstanden.
Es fehlen immer noch verlässliche Marker, die eine genaue Charakterisierung einzelner
Untergruppen zulässt. Vieles spricht dafür, dass Tumore aus einem kleinen Prozentsatz
CSC bestehen, die dann, im Sinne einer Hierarchie, in beliebig viele Zellen weiterdifferenzieren
können. Da diese Stammzellen sehr vielen Differenzierungs- und Redifferenzierungsschritten
unterworfen sind, geht es eher um die Beschreibung eines Fließgleichgewichtes. Die
Definition der einzelnen Stadien ist weitgehend unverstanden, ebenso wie die Faktoren
des Mikromilieus, die die einzelnen Differenzierungsschritte auslösen. Dennoch wird
gerade in diesen Fähigkeiten der Schlüssel zur Tumorinitiierung, Metastasierung und
Therapieresistenz vermutet. Bedeutsam sind die biologischen Funktionen und die damit
assoziierten Signalwege innerhalb der Zellen, wie z. B. das Self Renewal. Eine spezifische
Beeinflussung eines solchen Weges könnte auch für die Therapie solcher Zellen von
hohem Interesse sein. Aktuell gibt es hierzu nur vorläufige Überlegungen und einige
in vitro Testungen, die allerdings noch weit von einer translationalen klinischen
Umsetzung entfernt sind.
Abstract
Implication of Stem Cells in the Biology and Therapy of Head and Neck Cancer
Stem cells play a central role in re- and generation of tissues. Special importance
has been attributed to them in cancer biology. 2 entities can be discriminated: cancer
infiltrating stem cells and cancer initiating stem cells. Infiltrating stem cells
will be attracted to the tumor in order to be remodelled for tumor expansion, e. g.
endothelial cells or other cancerous tissue components, yet these cells are per se
benign. Malignant cancer stem cells are capable to generate a new tumor, histologically
identical with the cancer they originate from. Many steps in cancer stem cell biology
are not understood to date. It is still believed that CSC are only a minor cell fraction
in tumor but capable to differentiate in hierarchical manner into any other tissue
type. These stem cells are undergoing many steps of differentiation and dedifferentiation
in a steady state. The factors of the micromilieu contributing to this are largely
not understood. Still these steps are regarded as the key to tumorinitiation, metastases
and resistance to therapy. The biological functions and associated signaltransduction
pathways, e. g. self renewal pathways will be the key to future therapeutical strategies.
Schlüsselwörter
Stammzellen - Tumorstammzellen - EMT - WNT - Self Renewal
Key words
stem cells - cancer stem cells - WNT - EMT - self renewal
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Korrespondenzadresse
Prof. Dr. med. Barbara Wollenberg
Direktorin
Klinik für Hals-, Nasen- und
Ohrenheilkunde
Medizinische Fakultät Lübeck
Ratzeburger Allee 160
(Haus 28)
23538 Lübeck
Email: barbara.wollenberg@uk-sh.de
