Laryngorhinootologie 2011; 90: S110-S119
DOI: 10.1055/s-0030-1270442
Referat

© Georg Thieme Verlag KG Stuttgart · New York

Bedeutung von Stammzellen in der Biologie und Therapie von Kopf-Hals-Karzinomen

Implication of Stem Cells in the Biology and Therapy of Head and Neck CancerB. Wollenberg1
  • 1Klinik für Hals-, Nasen- und Ohrenheilkunde, Medizinische Fakultät Lübeck
Further Information

Publication History

Publication Date:
26 April 2011 (online)

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.

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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