2010
DOI: 10.1002/pros.21277
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Dickkopf‐1 (DKK‐1) stimulated prostate cancer growth and metastasis and inhibited bone formation in osteoblastic bone metastases

Abstract: Background Osteoblastic bone metastasis is the predominant phenotype observed in prostate cancer patients and is associated with high patient mortality and morbidity. However, the mechanisms determining the development of this phenotype are not well understood. Prostate cancer cells secrete several osteogenic factors including Wnt proteins, which are not only osteoinductive but also oncogenic. Therefore, the purpose of the study was to investigate the contribution of the Wnt signaling pathway in prostate cance… Show more

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Cited by 113 publications
(100 citation statements)
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“…Once CaP cells had invaded the bone, DKK-1 levels subsequently minimized as new bone formation required Wnt activation to propagate osteoblastic activity. This was in line with more recent experimental data showing that intercardiac injection of stably expressing DKK-1 Ace-1 cells (a CaP cell line that produces mixed osteoblastic and osteolytic lesions) into mice, increased the appearance of a subcutaneous tumor mass and decreased Ace-1-induced osteoblast activity (Thudi et al, 2011). Taken together, these results support the association between DKK-1 overexpression in CaP metastases and a decreased overall patient lifespan (Hall et al, 2008).…”
Section: Canonical Wnt Pathway and Cap Progressionsupporting
confidence: 90%
“…Once CaP cells had invaded the bone, DKK-1 levels subsequently minimized as new bone formation required Wnt activation to propagate osteoblastic activity. This was in line with more recent experimental data showing that intercardiac injection of stably expressing DKK-1 Ace-1 cells (a CaP cell line that produces mixed osteoblastic and osteolytic lesions) into mice, increased the appearance of a subcutaneous tumor mass and decreased Ace-1-induced osteoblast activity (Thudi et al, 2011). Taken together, these results support the association between DKK-1 overexpression in CaP metastases and a decreased overall patient lifespan (Hall et al, 2008).…”
Section: Canonical Wnt Pathway and Cap Progressionsupporting
confidence: 90%
“…Osteoblastic metastases tend to induce new woven bone on the surface of pre-existing medullary trabecular bone [15], which was observed in our model, both in untreated and in PDT-treated groups. Similar observations of overwhelming osteolysis in addition to definite areas of new bone formation have also been described in mouse models of mixed osteolytic/osteoblastic metastases [12,[16][17][18]. As such, it remains important to consider host bony repair mechanisms when considering the effect of tumor invasion of vertebrae bone.…”
Section: Discussionmentioning
confidence: 70%
“…DKK1 has been proposed to be an important regulator in prostate cancer bone metastasis because alterations in DKK1 expression are linked to several tumor types with a propensity to grow in bone including prostate carcinoma, breast carcinoma, and multiple myeloma (Forget et al 2007). Prostate cancer cells overexpressing DKK1 have a higher potential to metastasize into bone and generate osteolytic lesions (Thudi et al 2010). DKK1 upregulation is a frequent event in mammary cancer, and increased serum levels of DKK1 are associated with the presence of bone metastasis in patients (Voorzanger-Rousselot et al 2007;Bu et al 2008).…”
Section: Wnt In Bone Cancer and Metastasismentioning
confidence: 99%