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Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche?

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Abstract

Introduction

Early disease onset, clinical manifestation, histomorphology, and increased tendency to relapse distinguish the adamantinomatous craniopharyngioma (adaCP) from the more favorable papillary variant (papCP). A molecular hallmark of adaCP is the activated Wnt signaling pathway indicated by nuclear β-catenin accumulation in a subset of tumor cells. A mouse model recently illustrated that these cells are the driving force in tumorigenesis of adaCP. This observation and the peculiar growth pattern points to the existence of a specific tumor stem cell (TSC) population in human CP.

Materials and Methods

To prove this hypothesis, the TSC markers CD133 (Prominin1) and CD44 were examined in papCP (n = 8) and adaCP (n = 25) on mRNA level using quantitative real time PCR of total tumor RNA. Furthermore, we investigated protein expression performing immunohistochemical analyses of formalin-fixed paraffin embedded tumor samples.

Results

PapCP revealed a homogenous CD44 expression pattern predominantly at the cell membrane, whereas CD133 labeling was hardly detectable. In adaCP, on the other hand all markers were consistently and predominantly co-expressed in nuclear β-catenin accumulating cell clusters, which was confirmed by double immunofluorescence staining. Overall expression of CD44 was significantly decreased in adaCP versus papCP, whereas CD133 showed significantly higher protein and mRNA levels in adaCP.

Conclusions

Our results indicate tumor stem cell-like characteristics of β-catenin accumulating cell clusters in adaCP, which may represent a tumor stem cell niche and might contribute to tumor recurrence. The potential impact of these special cell groups in regard to future CP management, including postoperative follow-up and additional treatment remains to be explored.

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Acknowledgments

We are indebted to Tajana Jungbauer, Diana Maron and Birte Rings for conducting the immunohistochemical stainings. We thank Robyn Auer for proofreading the manuscript.

Ethical standards

A declaration of consent of each patient is available for all specimens for further scientific investigation, approved by the local ethics committee of the University Erlangen. Procedures were conducted in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neuropathology, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Annett Hölsken, Christina Stache & Rolf Buslei

  2. Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Sven Martin Schlaffer & Michael Buchfelder

  3. Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Jörg Flitsch

  4. International Neuroscience Institute, Rudolf-Pichlmayr-Straße 4, 30625, Hannover, Germany

    Rudolf Fahlbusch

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  1. Annett Hölsken
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  2. Christina Stache
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Correspondence to Annett Hölsken.

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Hölsken, A., Stache, C., Schlaffer, S.M. et al. Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche?. Pituitary 17, 546–556 (2014). https://doi.org/10.1007/s11102-013-0543-8

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