Die Tumorstammzellnische im Kopf-Hals-Bereich – Knotenpunkt mit therapeutischem Potenzial?

Zusammenfassung

In den letzten Jahren verdichten sich Hinweise, dass eine Tumorstammzellpopulation in Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC) existiert. Man vermutet, dass diese Tumorstammzellen (CSC) über Selbsterneuerungskapazität verfügen und für Wachstum, Metastasierung, Rekurrenz und Therapieresistenz des Tumors essenziell sind. Stammzellen werden von einer spezialisierten zellulären und nichtzellulären Mikroumgebung unterstützt, die „Stammzellnische“ genannt wird. Eine mögliche Strategie, um CSC zu attackieren, könnte eine Beeinflussung ihrer Nische sein.

Stromal cell-derived factor-1 (SDF-1) gilt als Schlüsselregulator des Zellverkehrs zwischen Nische und der peripheren Blutzirkulation. SDF-1 ist ein multifunktionelles Zytokin, das u. a. von Endothel-/Stromazellen sezerniert wird. Als sein Rezeptor wurde der 7-Transmembranrezeptor CXCR4 identifiziert. Die SDF-1-CXCR4-Achse ist ein wesentlicher Faktor für Migration und Mobilisation von CSC in und aus ihrer Nische. Ihre Existenz und Funktionalität in der Tumorstammzellnische von HNSCC konnte bereits nachgewiesen werden. Strategien, die in diese Interaktion eingreifen, könnten einen entscheidenden Beitrag in der Therapie von HNSCC bieten.

Um Mechanismen in der Tumorstammzellnische von HNSCC in vitro zu untersuchen, werden Modelle benötigt. Wir erwarten, dass die 3D-Zellkultur und das 3D-Bioprinting bei der Entwicklung neuer, individualisierter Therapiestrategien bahnbrechenden Charakter aufweisen werden.

Hier geben wir eine Übersicht über den Wissensstand hinsichtlich der Interaktionen in der Tumorstammzellnische von HNSCC am Beispiel der SDF-1-CXCR4-Achse.

Abstract

An increasing amount of evidence suggests the existence of a stem cell-like population in head and neck squamous cell carcinoma (HNSCC). These cells have been termed cancer stem cells (CSC) due to the shared properties with somatic stem cells, such as the ability to self-renew and differentiate. Furthermore, the CSC are thought to be resistant to antineoplastic treatments and are therefore clinically relevant. As with somatic stem cells, CSC are thought to reside in a specialized supportive microenvironment, called the stem cell niche. One possible strategy to target the CSC could be through affecting functions of the stem cell niche.

Stromal cell-derived factor-1 (SDF-1) is a multifunctional cytokine, which is secreted by e. g. stromal cells within the niche. SDF-1 is known to be the major regulator of stem cell trafficking between the niche and the peripheral vascular system. It elicits the chemotactic activity through interaction with a transmembrane receptor CXCR4, expressed by CSC. The SDF-1-CXCR4-axis is thought to play a crucial role in the interaction between CSC and their supportive cells in the tumor niche. A better understanding of these interactions could help in gaining further insight into the pathophysiology of progression/recurrence of malignant diseases and aid in finding new strategies for therapy.

Specialized cell culture models are of advantage for deciphering the mechanisms of interaction between CSC and their niche. We anticipate that the recent technological advancements in bioprinting and the development of complex 3D cell culture model systems will contribute to our understanding of these mechanisms and to the establishment of individualized therapies.

Here were provide an overview of the current knowledge on the CSC-tumor stem cell niche interactions in HNSCC with a focus on the SDF-1-CXCR4 axis.

Schlüsselwörter

Tumorstammzellen - Tumorstammzellnische - Plattenepithelkarzinom - Kopf-Hals - SDF1

Key words

cancer stem cells - cancer stem cell niche - squamous cell carcinoma - head and neck - SDF1

Publication History

Received: 08 February 2020

Accepted: 09 September 2020

Article published online:
05 January 2021

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