Increased Dickkopf-1 expression in breast cancer bone metastases

Abstract

The aim of this study was to determine whether Dickkopf-1 (Dkk-1) expression in breast cancer was associated with bone metastases. We first analysed Dkk-1 expression by human breast cancer cell lines that induce osteolytic or osteoblastic lesions in animals. Dickkopf-1 levels were then measured in the bone marrow aspirates of hind limbs from eight NMRI mice inoculated with breast cancer cells that induced bone metastases and 11 age-matched non-inoculated control animals. Finally, Dkk-1 was measured in the serum of 17 women with breast cancer in complete remission, 19 women with breast cancer and bone metastases, 16 women with breast cancer and metastases at non-bone sites and 16 healthy women. Only breast cancer cells that induce osteolytic lesions in animals produced Dkk-1. There was a six-fold increase in Dkk-1 levels in the bone marrow from animals inoculated with MDA-B02 cells when compared with that of control non-inoculated animals (P ¼ 0.003). Median Dkk-1 levels in the serum of patients with breast cancer and bone metastases were significantly higher than levels of patients in complete remission (P ¼ 0.016), patients with breast cancer having metastases at non-bone sites (Po0.0001) and healthy women (P ¼ 0.047), although there was a large overlap in individual levels between the different groups. In conclusion, Dkk-1 is secreted by osteolytic human breast cancer cells lines and increased circulating levels are associated with the presence of bone metastases in patients with breast cancer. Measurements of circulating Dkk-1 levels may be useful for the clinical investigation of patients with breast cancer and bone metastases.

Bone metastases in gastric cancer follow a RANKL-independent mechanism

“…We detected DKK-1 expression in primary tumor, according to previously published data reporting its expression in some human specimens of tumors, and suggesting that a cancermediated modulation of WNT activity affects the metastatic phenotype (37)(38)(39). SOST was only detected in bone metastatic samples, according to the specific expression of these molecules by bone cells (34).…”

High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

“…(12) Osteoporosis-related fractures (ORFs) have major social and economic impacts, with serious morbidities and increased mortality following hip and vertebral fractures. (13,14) We hypothesized that postmenopausal women with higher circulating sclerostin levels have a greater ORF risk. The main objective of this study was to investigate the role of circulating sclerostin levels in relation to bone turnover markers (BTMs) in predicting ORF occurrence in a prospective cohort of postmenopausal women.…”

Dysregulation of Wnt Signaling in Breast Cancer

“…Indeed, Dkk1 is highly expressed in several breast cancer cell lines, including the MDA-MB-231 (osteolytic) and MCF-7 (osteolytic and osteoblastic) cell lines (Forget et al, 2007;Pinzone et al, 2009;Bu et al, 2008). Additionally, serum Dkk1 levels were elevated in patients with metastasized breast cancer in the bone compared to patients who were in complete remission (Voorzanger-Rousselot et al, 2007). Dkk1-mediated bone metastasis in breast cancer patients is likely to occur as a result of Dkk1 acting as a molecular switch, which decreases osteoblastogenesis and increases osteolysis (Fig.…”