Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone

Li, Z. G.; Yang, J.; Vazquez, E. S.; Rose, D.; Vakar-Lopez, F.; Mathew, P.; Lopez, A.; Logothetis, C. J.; Lin, S.-H.; Navone, N. M.
January 2008
Oncogene;1/24/2008, Vol. 27 Issue 5, p596
Academic Journal
The tendency of prostate cancer to produce osteoblastic bone metastases suggests that cancer cells and osteoblasts interact in ways that contribute to cancer progression. To identify factors that mediate these interactions, we compared gene expression patterns between two bone-derived prostate cancer cell lines that produce osteoblastic (MDA PCa 2b) or osteolytic lesions (PC-3). Both cell lines expressed Wnt ligands, including WNT7b, a canonical Wnt implicated in osteogenesis. PC-3 cells expressed 50 times more Dickkopf-1 (DKK1), an inhibitor of Wnt pathways, than did MDA PCa 2b cells. Evaluation of the functional role of these factors (in cocultures of prostate cancer cells with primary mouse osteoblasts (PMOs) or in bone organ cultures) showed that MDA PCa 2b cells activated Wnt canonical signaling in PMOs and that DKK1 blocked osteoblast proliferation and new bone formation induced by MDA PCa 2b cells. MDA PCa 2b cells did not induce bone formation in calvaria from mice lacking the Wnt co-receptor Lrp5. In human specimens, WNT7b was not expressed in normal prostate but was expressed in areas of high-grade prostate intraepithelial neoplasia, in three of nine primary prostate tumor specimens and in 16 of 38 samples of bone metastases from prostate cancer. DKK1 was not expressed in normal or cancerous tissue but was expressed in two of three specimens of osteolytic bone metastases (P=0.0119). We conclude that MDA PCa 2b induces new bone formation through Wnt canonical signaling, that LRP5 mediates this effect, and that DKK1 is involved in the balance between bone formation and resorption that determines lesion phenotype.Oncogene (2008) 27, 596–603; doi:10.1038/sj.onc.1210694; published online 13 August 2007


Related Articles

  • A parathyroid-hormone-related-protein (PTH-rP)-specific cytotoxic T cell response induced by in vitro stimulation of tumour-infiltrating lymphocytes derived from prostate cancer metastases, with epitope peptide-loaded autologous dendritic cells and... Correale, P; Micheli, L; Vecchio, M T Del; Sabatino, M; Petrioli, R; Pozzessere, D; Marsili, S; Giorgi, G; Lozzi, L; Neri, P; Francini, G // British Journal of Cancer;12/1/2001, Vol. 85 Issue 11, p1722 

    Bone metastases are one of the most common events in patients with prostate carcinoma. PTH-rP, a protein produced by prostate carcinoma and other epithelial cancers, is a key agent for the development of bone metastases. A PTH-rP-derived peptide, designated PTR-4 was identified, which is capable...

  • Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Garnero, P; Buchs, N; Zekri, J; Rizzoli, R; Coleman, R E; Delmas, P D // British Journal of Cancer;2/15/2000, Vol. 82 Issue 4, p858 

    Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation...

  • The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/ Blastic Bone Lesions Observed in Metastatic Prostate Cancer. Al Nakouzi, Nader; Bawa, Olivia; Le Pape, Alain; Lerondel, Stéphanie; Gaudin, Catherine; Opolon, Paule; Gonin, Patrick; Fizazi, Karim; Chauchereau, Anne // Neoplasia;May2012, Vol. 14 Issue 5, p376 

    Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models...

  • Prioritizing genes associated with prostate cancer development. Gorlov, Ivan P.; Sircar, Kanishka; Hongya Zhao; Maity, Sankar N.; Navone, Nora M.; Gorlova, Olga Y.; Troncoso, Patricia; Pettaway, Curtis A.; Jin Young Byun; Logothetis, Christopher J. // BMC Cancer;2010, Vol. 10, p599 

    Background: The genetic control of prostate cancer development is poorly understood. Large numbers of geneexpression datasets on different aspects of prostate tumorigenesis are available. We used these data to identify and prioritize candidate genes associated with the development of prostate...

  • Impact of tumor cytoreduction in metastatic prostate cancer. Sow, Yaya; Sow, Ousmane; Fall, Boubacar; Sine, Babacar; Sarr, Alioune; Ondo, Cyrille Zé; Diao, Babacar; Ndoye, Alain Khassim; Ba, Mamadou // Research & Reports in Urology;May2019, Vol. 11, p137 

    Highlights from the article: Cally (36 patients (35.3%) in group 1 and 25 patients Treatments offerbeneficial effect tothe patients by improv- Brachytherapy treatment improves patient survival com- Including the smaller number of patient, the short patient For local treatment of the primary...

  • Should bisphosphonates be used routinely in patients with prostate cancer metastatic to bone? Canil, Christina M.; Tannock, Ian F. // JNCI: Journal of the National Cancer Institute;10/2/2002, Vol. 94 Issue 19, p1422 

    Examines the role of biphosphonates in treating patients with prostate cancer metastatic to bone. Primary modality of treatment for patients with metastatic prostate cancer; Uncertainty of biphosphonate in preventing events related to osteoblastic metastases; Efficacy of pamidronate in reducing...

  • The Role of α [sub v]β[sub 3] in Prostate Cancer Progression. Cooper, Carlton R.; Chay, Christopher H.; Pienta, Kenneth J. // Neoplasia;May/Jun2002, Vol. 4 Issue 3, p191 

    Discusses the role of integrin α[subv]β[sub3] in prostate cancer progression. Significance of the role of integrins in prostate tumor progression; Functions of the integrin; Importance of cell adhesion molecules for the preferential metastasis of prostate cancer to bone.

  • Analysis of the Lipid Profile and Atherogenic Risk during Androgen Deprivation Therapy in Prostate Cancer Patients. Salvador, C.; Planas, J.; Agreda, F.; Placer, J.; Trilla, E.; Lopez, M.A.; Morote, J. // Urologia Internationalis;Jan2013, Vol. 90 Issue 1, p41 

    Objective: To analyse changes in lipid profiles observed in patients receiving androgen deprivation therapy (ADT) and to evaluate differences between medical castration and maximal androgen blockade (MAB). Material and Methods: Serum levels of total cholesterol (TC), high-density lipoproteins...

  • Let-7 MicroRNA Family Is Selectively Secreted into the Extracellular Environment via Exosomes in a Metastatic Gastric Cancer Cell Line. Ohshima, Keiichi; Inoue, Kanako; Fujiwara, Akemi; Hatakeyama, Keiichi; Kanto, Kaori; Watanabe, Yuko; Muramatsu, Koji; Fukuda, Yorikane; Ogura, Shun-ichiro; Yamaguchi, Ken; Mochizuki, Tohru // PLoS ONE;2010, Vol. 5 Issue 10, p1 

    Background: Exosomes play a major role in cell-to-cell communication, targeting cells to transfer exosomal molecules including proteins,mRNAs, and microRNAs (miRNAs) by an endocytosis-like pathway.miRNAs are small noncoding RNA molecules on average 22 nucleotides in length that regulate numerous...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics