Cancer Cell Biology
You have full text access to this OnlineOpen article
Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases
Article first published online: 10 JUN 2008
DOI: 10.1002/ijc.23625
Copyright © 2008 Wiley-Liss, Inc.
Additional Information
How to Cite
Bu, G., Lu, W., Liu, C.-C., Selander, K., Yoneda, T., Hall, C., Keller, E. T. and Li, Y. (2008), Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases. Int. J. Cancer, 123: 1034–1042. doi: 10.1002/ijc.23625
Publication History
- Issue published online: 17 JUN 2008
- Article first published online: 10 JUN 2008
- Manuscript Accepted: 13 MAR 2008
- Manuscript Received: 29 AUG 2007
Funded by
- American Heart Association. Grant Number: 0330118N
- National Institutes of Health. Grant Numbers: P01 CA093900, RO1 CA100520
References
- 1,. Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2002; 2: 389–406.
- 2,,,,,,,,,,,, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93: 165–76.
- 3,,,,,,,,,,,, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998; 95: 3597–602.
- 4,,,. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 2006; 12: 17–25.
- 5,,. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 2003; 1653: 1–24.
- 6,. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004; 20: 781–810.
- 7,,,. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: arrows point the way. Development 2004; 131: 1663–77.
- 8,,,. WNT and β-catenin signalling: diseases and therapies. Nat Rev Genet 2004; 5: 691–701.
- 9,,. Regulation of bone mass by Wnt signaling. J Clin Invest 2006; 116: 1202–9.
- 10,,,. Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 2005; 8: 739–50.
- 11,,,,. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 2005; 8: 727–38.
- 12,,,,,,,,. Essential role of β-catenin in postnatal bone acquisition. J Biol Chem 2005; 280: 21162–8.
- 13,,,,,,,,,,. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 2005; 8: 751–64.
- 14,,,,. Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci 2006; 119: 1283–96.
- 15,,,,,,. Gene array analysis of Wnt-regulated genes in C3H10T1/2 cells. Bone 2005; 36: 585–98.
- 16. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002; 2: 584–93.
- 17. Mechanisms of bone metastasis. N Engl J Med 2004; 350: 1655–64.
- 18,. Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia 2005; 10: 169–80.
- 19,,,,,,, The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003; 349: 2483–94.
- 20,,,,. Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res 2005; 65: 7554–60.
- 21,,,,,. A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem Cells 2006; 24: 986–91.Direct Link:
- 22,,,,,,,. Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 2006; 119: 1728–31.Direct Link:
- 23,,,,,, Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 2007; 109: 2106–11.
- 24,,,,,,,,. Dickkopf homolog 1 mediates endothelin-1-stimulated new bone formation. Mol Endocrinol 2007; 21: 486–98.
- 25,,,,,,,,,,,. Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 2006; 135: 688–92.Direct Link:
- 26,,,,,,,,,, The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Blood 2007; 109: 4470–7.
- 27,,,,,,,,,,,. Lack of noggin expression by cancer cells is a determinant of the osteoblast response in bone metastases. Am J Pathol 2007; 170: 160–75.
- 28,. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982; 31: 99–109.
- 29,,,. Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors. Cell 1983; 33: 369–77.
- 30,,,,. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature 1984; 307: 131–6.
- 31,,,,,,,,. Compartment switching of WNT-2 expression in human breast tumors. Cancer Res 1996; 56: 4320–3.
- 32,,,,. Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue. Cancer Res 1994; 54: 2615–21.
- 33,,,,. Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. Br J Cancer 1997; 75: 1131–6.
- 34,,,,,,,,,,. WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type. Oncogene 2001; 20: 5810–7.
- 35,,,,,,,. Gene expression profiling of breast cancers with emphasis of β-catenin regulation. J Korean Med Sci 2004; 19: 275–82.
- 36,,,,,,,. β-Catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci USA 2000; 97: 4262–6.
- 37,. Significance of E-cadherin/β-catenin complex and cyclin D1 in breast cancer. Oncol Rep 2002; 9: 915–28.
- 38,,,,,,,. β-Catenin and p53 analyses of a breast carcinoma tissue microarray. Cancer 2004; 100: 2084–92.Direct Link:
- 39,,,,,,,,,,. Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc Natl Acad Sci USA 2006; 103: 3799–804.
- 40,,,,,. E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model. Cancer Res 1996; 56: 4063–70.
- 41,. Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG. RANKL and M-CSF. Mol Cancer 2007; 6: 71.
- 42,,,,. Characterization of Wnt-1 and Wnt-2 induced growth alterations and signaling pathways in NIH3T3 fibroblasts. Oncogene 1998; 16: 2819–25.
- 43,,,,. An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells. Cancer Cell 2004; 6: 497–506.
- 44,. Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway. J Cell Biochem 2005; 95: 328–38.Direct Link:
- 45,,,,,,,. Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res 1995; 55: 3551–7.
- 46,,,,,,. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest 1997; 99: 2509–17.
- 47,,,,,,,. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003; 3: 537–49.
- 48,,,,. A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro. J Bone Miner Res 2001; 16: 1486–95.Direct Link:
- 49,,,,,,. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology 1999; 140: 4451–8.
- 50,,. Osteoblast-derived oxysterol is a migration-inducing factor for human breast cancer cells. J Biol Chem 2003; 278: 25376–85.
- 51,,,,,,,,,,,, et al. Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-kappaB ligand pathway. Cancer Res 2005; 65: 11001–9.
- 52,,,,,,,. Osteoprotegerin overexpression by breast cancer cells enhances orthotopic and osseous tumor growth and contrasts with that delivered therapeutically. Cancer Res 2006; 66: 3620–8.
- 53,,,,,,,. DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway. Oncogene 2004; 23: 8520–6.
- 54,,,,,,,,. The Wnt antagonist DICKKOPF-1 gene is a downstream target of β-catenin/TCF and is downregulated in human colon cancer. Oncogene 2005; 24: 1098–103.
- 55,,,,,. FGF-20 and DKK1 are transcriptional targets of β-catenin and FGF-20 is implicated in cancer and development. EMBO J 2005; 24: 73–84.
- 56,,,,,,,,,,,, et al. Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/β-catenin signaling is activated in human colon tumors. Proc Natl Acad Sci USA 2001; 98: 14973–8.
- 57,,,,,. Wnt/β-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 2002; 22: 1172–83.
- 58,,,,,,,,,,. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol 2002; 22: 1184–93.
- 59,,,,,,,. Activation of AXIN2 expression by β-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling. J Biol Chem 2002; 277: 21657–65.
- 60,,,. A novel mechanism for Wnt activation of canonical signaling through the LRP6 receptor. Mol Cell Biol 2003; 23: 5825–35.
- 61,,,,,,,. The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br J Cancer 2007; 96: 646–53.
- 62,,,,,,,,,,,, et al. Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas. Cancer Res 2007; 67: 2517–25.
- 63,,,,,,,,. Overexpression of human Dickkopf-1, an antagonist of wingless/WNT signaling, in human hepatoblastomas and Wilms tumors. Lab Invest 2003; 83: 429–34.

1097-0215/asset/olbannerleft.jpg?v=1&s=45719cd7de57873027993264fcc568b335a8cd56)
1097-0215/asset/olbannerright.jpg?v=1&s=5e0fba63c1309b3036eb9215a0e1e83dd02efd19)
