DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis

Translational Oncology
Katrina L Clines, Gregory A Clines

Abstract

Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis. LnCaP, C4-2B, LuCaP23.1, T47D, ZR-75-1, MCF-7, ARCaP and ARCaPM cancer cells that generate osteoblastic, mixed or no bone lesions had the lowest DKK1 expression. The cell lines with negligible expression, LnCaP, C4-2B and T47D, exhibited methylation of the DKK1 promoter. Canonical Wnt signaling activity was then determined and found in all cell lines tested, even in the MDA-MB-231 and PC3 cell lines despite sizeable amounts of DKK1 protein expression expected to block canonical Wnt signaling. A mechanism of DKK1 resistance in the osteolytic cell lines was investigated and determine...Continue Reading

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Citations

Oct 10, 2019·Biomarkers in Medicine·Zahra Sadat HashemiMohamad Javad Rasaee
May 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shian-Ren LinYen-Nien Liu
Jan 26, 2021·Frontiers in Oncology·Beibei ChenXiao-Bing Chen

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