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.
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We declare that we have no conflict of interest.
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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