The Wnt inhibitor Dickkopf-1; a link between breast cancer and bone metastases

Background: Breast cancer is the second leading cause of cancer deaths in women and metastasizes to bone in greater than 80% of patients with advanced disease. Many mechanisms have been implicated in breast cancer metastases to bone. The critical role of the Wnt signalling pathway inhibition in sustaining the onset of bone lesions has been demonstrated in a variety of bone diseases and tumors. Over expression of dickkopf-1 (Dkk1) protein, a negative regulator of the Wnt/β-catenin pathway, has been found in breast cancer cell lines and in patients with breast cancer and bone metastasis. Further understanding of the mechanistic role of Dkk1 as a link between primary breast tumor and secondary osteolytic bone metastasis may enable promising tool for breast cancer bone metastases immunotherapy.

Materials and methods: 133 subjects were enrolled in this study including 59 healthy women and 74 breast cancer patients with or witout bone metastasis.

Serum level of Dkk1 was tested using Human Dkk1 Quantikine ELISA Kit. Gene expression of Dkk1 was tested using RT-PCR.

Results and conclusion: Serum level of Dkk1 was significantly higher in breast cancer patients compared to healthy controls. Interestingly, serum Dkk1 level was higher in patients with bone metastasis, suggesting that Dkk1 may promote metastasis. In light of current clinical trials evaluating the efficacy of anti-DKK1 antibody therapies in multiple myloma and solid malignancies, the measurement of DKK1 circulating Dkk1 levels in breast cancer patients with bone metastasis may gain clinical relevance.

Results of PCR test will be shown later.