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Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis

T Byun1, M Karimi, J L Marsh

  • 1Division of Hematology/Oncology, University of California, Irvine Medical Center, 101 The City Drive, Bld 23, Rm 244, Orange, CA 92868, USA.

Journal of Clinical Pathology
|April 29, 2005
PubMed
Abstract

Insights

Soluble Wnt antagonists (sWAs) show distinct expression patterns in the upper and lower gastrointestinal tracts. Loss of FrzB in gastric cancer suggests a tumor suppressor role, while other sWAs may maintain stem cell pools.

Area of Science:

  • Gastroenterology
  • Oncology
  • Molecular Biology

Background:

  • Wnt signaling pathway dysregulation is linked to gastric and colon cancers.
  • Soluble Wnt antagonists (sWAs), including dickkopf (Dkk) proteins and Wnt inhibitory factor-1 (Wif1), modulate Wnt signaling initiation.

Purpose of the Study:

  • To investigate the role of sWAs in tumorigenesis of the upper (gastric) and lower (colon) gastrointestinal tracts.

Main Methods:

  • In situ RNA hybridization was used to assess the expression of Dkk1-3, Wif1, and FrzB in normal and cancerous human gastric and colon tissues.
  • Expression levels were semiquantitatively graded.

Main Results:

  • Wif1, Dkk1, and Dkk2 were absent in normal gastric tissue, while Dkk3 and FrzB showed varied expression.
  • Dkk1 and FrzB were not detected in normal colon, whereas Wif1, Dkk3, and Dkk2 were expressed, particularly at crypt bases.
  • No significant differences in sWA expression were observed between malignant colon and matched normal tissues.

Conclusions:

  • sWA expression profiles differ between the gastric and colon tissues.
  • Loss of FrzB in gastric cancer indicates a potential tumor suppressor function.
  • Differential expression of Dkk2, Dkk3, and Wif1 in colonic crypts suggests their role in regulating Wnt signaling and maintaining the gastrointestinal stem cell pool.

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