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Hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation

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Abstract

The Hedgehog (Hh) pathway is a main regulation cascade in embryonic differentiation. It is also present in adult tissues and unusual expression has been associated with formation of benign and malignant lesions. We examined the presence of the Hedgehog pathway in normal and pathological human colon tissue. Components investigated include Sonic (Shh), Indian (Ihh), and Desert Hedgehog (Dhh), Gli1, Gli2, Gli3, and Patched (Ptch). Pathological tissue samples comprised 23 benign and 20 malignant lesions of human colon. The influence of the Hedgehog pathway on differentiation and proliferation has been investigated by analyzing the effect of the pathway inhibitor Cyclopamine on human colon cancer cell lines HT29 and CaCo2. In normal colon, we detected expression of Shh and Dhh within the lining epithelium and Patched, Gli1, and Gli2 along the whole crypts. Within all benign lesions, positive staining of Shh, Dhh, Gli1, Gli2, and Ptch was detected. Expression of Shh and Dhh was restricted to single cell aggregates. Malignant lesions also displayed focal staining pattern for Shh and Dhh but to a much lesser extent. We conclude that Hedgehog signaling is involved rather in constant differentiation and renewing of the colonic lining epithelium than in cancer formation, growth, or proliferation.

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Abbreviations

CRC:

Colorectal cancer

Shh:

Sonic Hedgehog

Ihh:

Indian Hedgehog

Dhh:

Desert Hedgehog

FFPE:

Formalin-fixed paraffin-embedded

CK:

Cytokeratin

Hh:

Hedgehog

APC:

Adenomatous polyposis coli

EGFR:

Epidermal growth factor receptor

Ptch:

Patched

Smo:

Smoothened

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

DMSO:

Dimethyl sulfoxide

PBS:

Phosphate-buffered saline

HIER:

Heat-induced epitope retrieval

NE:

Neuroendocrine

TMA:

Tissue microarray

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Acknowledgments

This study was supported by the Österreichische Krebshilfe and PMU Salzburg research grant. TK is supported by a research grant of the Österreichische Nationalbank (project No. 12677). We hereby declare that all experiments described in this study comply with the current laws in Austria.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, General Hospital, Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020, Salzburg, Austria

    Beate Alinger, Felix Strasser, Otto Dietze & Cornelia Hauser-Kronberger

  2. Department of Internal Medicine I, Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020, Salzburg, Austria

    Tobias Kiesslich & Frieder Berr

  3. Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of Paracelsus Medical University Salzburg, Paracelsusstraße 37, 5110, Oberndorf, Austria

    Christian Datz

  4. Department of Molecular Biology, University of Salzburg, Hellbrunnerstraße 34, 5020, Salzburg, Austria

    Fritz Aberger

  5. Department of Pathology, Vienna Medical University, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Klaus Kaserer

Authors
  1. Beate Alinger
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  2. Tobias Kiesslich
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  3. Christian Datz
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  4. Fritz Aberger
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  5. Felix Strasser
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  7. Otto Dietze
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  8. Klaus Kaserer
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  9. Cornelia Hauser-Kronberger
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Corresponding author

Correspondence to Cornelia Hauser-Kronberger.

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Alinger, B., Kiesslich, T., Datz, C. et al. Hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation. Virchows Arch 454, 369–379 (2009). https://doi.org/10.1007/s00428-009-0753-7

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  • DOI: https://doi.org/10.1007/s00428-009-0753-7

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