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In this prospectus, we describe our research on Wnt and the CaP bone phenotype. Wnts are cysteine\u2010rich glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Wnts have been shown to have autocrine tumor effects, such as enhancing proliferation and protecting against apoptosis. In addition, we have recently identified that CaP\u2010produced Wnts act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. In addition to Wnts, CaP cells express the soluble Wnt inhibitor dickkopf\u20101 (DKK\u20101). It appears that DKK\u20101 production occurs early in the development of skeletal metastases, which results in masking of osteogenic Wnts, thus favoring osteolysis at the metastatic site. As metastases progress, DKK\u20101 expression decreases allowing for unmasking of Wnt's osteoblastic activity and ultimately resulting in osteosclerosis at the metastatic site. We believe that DKK\u20101 is one of the switches that transitions the CaP bone metastasis activity from osteolytic to osteoblastic. Wnt\/DKK\u20101 activity fits a model of CaP\u2010induced bone remodeling occurring in a continuum composed of an osteolytic phase, mediated by receptor activator of NFkB ligand (RANKL), parathyroid hormone\u2010related protein (PTHRP) and DKK\u20101; a transitional phase, where environmental alterations promote expression of osteoblastic factors (Wnts) and decreases osteolytic factors (i.e., DKK\u20101); and an osteoblastic phase, in which tumor growth\u2010associated hypoxia results in production of vascular endothelial growth factor and endothelin\u20101, which have osteoblastic activity. This model suggests that targeting both osteolytic activity and osteoblastic activity will provide efficacy for therapy of CaP bone metastases. J. Cell. Biochem. 97: 661\u2013672, 2006. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20735","type":"journal-article","created":{"date-parts":[[2006,1,30]],"date-time":"2006-01-30T16:48:22Z","timestamp":1138639702000},"page":"661-672","source":"Crossref","is-referenced-by-count":142,"title":["Role of wnts in prostate cancer bone metastases"],"prefix":"10.1002","volume":"97","author":[{"given":"Christopher L.","family":"Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ormond A.","family":"MacDougald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan T.","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1950)3:1<74::AID-CNCR2820030111>3.0.CO;2-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.6.960"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35083081"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408742102"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0498"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20284"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0060333"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013444"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65204-2"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/hp.2000.6698"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.1.87"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306972200"},{"key":"e_1_2_7_14_1","first-page":"308","article-title":"Tumor\u2010bone cellular interactions in skeletal metastases","volume":"4","author":"Chirgwin JM","year":"2004","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"e_1_2_7_15_1","first-page":"927","article-title":"Wnt signalling during limb development. 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