Wnt-5a protein expression in primary dukes B colon cancers identifies a subgroup of patients with good prognosis.

Abstract

Oncogenic Wnt/beta-catenin signaling occurs in a majority of colorectal cancers. In contrast, very little is known about the role of the nontransforming Wnt protein family member Wnt-5a in those tumors. In the most common of the three colon cancer stages, Dukes B or lymph node-negative, the outcome is the hardest to predict. We searched for a predictive marker in this group and observed loss of or reduced Wnt-5a expression in 50% of Dukes B tumors. Such Wnt-5a negativity was a strong predictor of adverse outcome, with a relative risk of death of 3.007 (95% confidence interval, 1.336-6.769; P = 0.008) after 5 years in Wnt-5a-negative patients. Furthermore, the median survival time after diagnosis was 109.1 months for patients with Wnt-5a-positive primary tumors but only 58 months for those with Wnt-5a-negative primary tumors. To find a possible biological explanation for these results, we studied the invasive and poorly differentiated human colon cancer cell line, SW480, which does not express Wnt-5a protein and the Wnt-5a-expressing and moderately differentiated Caco2 colon cancer cell line. We found that the addition of recombinant/purified Wnt-5a significantly reduced the migratory capacity of SW480 cells. By comparison, equivalent treatment did not significantly alter migration in the Wnt-5a-expressing Caco2 colon cancer cell line. These findings indicate that the expression of Wnt-5a in primary Dukes B colon cancer tissue constitutes a good prognostic marker for longer survival, which can be explained by the ability of Wnt-5a to impair tumor cell migration and thus reduce invasiveness and metastasis.

• Authors: Janna Dejmek, Annika Dejmek, Annette Säfholm, Anita Sjölander, Tommy Andersson
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 20 Pg. 9142-6 (Oct 15 2005) ISSN: 0008-5472 [Print] United States
• PMID: 16230369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins
• WNT5A protein, human
• Wnt Proteins
• Wnt-5a Protein

Topics

• Aged
• Cell Line, Tumor
• Colonic Neoplasms (metabolism, pathology)
• Female
• Humans
• Immunohistochemistry
• Male
• Neoplasm Staging
• Prognosis
• Proto-Oncogene Proteins (biosynthesis)
• Wnt Proteins (biosynthesis)
• Wnt-5a Protein