Abstract
Background: Dickkopf-1 (Dkk-1) glycoprotein is an inhibitor of the canonical Wnt pathway. Recent studies have demonstrated elevated Dkk-1 serum levels in patients with diverse malignancies. In vitro studies with melanoma cell lines showed that loss of Dkk-1 expression may contribute to tumor progression. Objective: The present study is the first in vivo investigation of Dkk-1 serum levels in patients with cutaneous malignant melanoma. Methods: We analyzed serum levels of Dkk-1 protein in 82 patients with cutaneous melanoma. Results: Serum levels were significantly increased (mean 83.01 pmol/l) in comparison to healthy controls (mean 29.36 pmol/l). No statistical difference in Dkk-1 serum levels neither between patients without or with lymph node metastases (p = 0.719) nor between patients with or without visceral metastases (p = 0.929) was found. Patients before excision had moderately higher Dkk-1 serum levels than after excision or with florid metastases. Conclusion: Our data suggest that increased Dkk-1 expression is an early event in melanoma, decreasing in later tumor stages. It was shown previously that Dkk-1 activates cell death in melanoma cells. Our in vivo data indicate that a decrease in Dkk-1 could be a sign of loss of tumor control.
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