{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:09:06Z","timestamp":1792782546387,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,10,28]],"date-time":"2009-10-28T00:00:00Z","timestamp":1256688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Office of Research and Development Medical Research Service"},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Defense Consortium","award":["DAMD170320033"],"award-info":[{"award-number":["DAMD170320033"]}]},{"name":"PO1 National Institutes of Health grant","award":["PO1CA085859"],"award-info":[{"award-number":["PO1CA085859"]}]},{"name":"Pacific Northwest Prostate Cancer SPORE","award":["P50CA097186"],"award-info":[{"award-number":["P50CA097186"]}]},{"name":"Richard M. Lucas Foundation","id":[{"id":"https:\/\/ror.org\/01s45wz62","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Prostate cancer (PCa) has a propensity to metastasize to bone. Tumor cells replace bone marrow and can elicit an osteoblastic, osteolytic, or mixed bone response. Our objective was to elucidate the mechanisms and key factors involved in promoting osteoclastogenesis in PCa bone metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We cultured osteoblast\u2010like MC3T3\u2010E1 cells with conditioned medium (CM) from PC\u20103 and C4\u20102B cells. MC3T3\u2010E1 mineralization decreased in the presence of PC\u20103 CM, whereas C4\u20102B CM had no effect on mineralization. Using oligo arrays and validating by real\u2010time PCR, we observed a decrease in the expression of mineralization\u2010associated genes in MC3T3\u2010E1 cells grown in the presence of PC\u20103 CM. In addition, PC\u20103 CM induced the expression of osteoclastogenesis\u2010associated genes IGFBP\u20105, IL\u20106, MCP\u20101, and RANKL while decreasing OPG expression in MC3T3\u2010E1 cells. Furthermore, CM from MC3T3\u2010E1 cells cultured in the presence of PC\u20103 CM, in association with soluble RANKL, increased osteoclastogenesis in RAW 264.7 cells. Investigation of PCa metastases and xenografts by immunohistochemistry revealed that the osteoclastic factor IL\u20106 was expressed in the majority of PCa bone metastases and to a lesser extent in PCa soft tissue metastases. In vitro it was determined that soluble IL\u20106R (sIL\u20106R) was necessary for IL\u20106 to inhibit mineralization in MC3T3\u2010E1 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>PC\u20103 cells inhibit osteoblast activity and induce osteoblasts to produce osteoclastic factors that promote osteoclastogenesis, and one of these factors, IL\u20106, is highly expressed in PCa bone metastases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>IL\u20106 may have an important role in promoting osteoclastogenesis in PCa bone metastasis through its' interaction with sIL\u20106R. Prostate 70: 412\u2013424, 2010. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.21075","type":"journal-article","created":{"date-parts":[[2009,10,28]],"date-time":"2009-10-28T09:23:51Z","timestamp":1256721831000},"page":"412-424","source":"Crossref","is-referenced-by-count":37,"title":["The expression of osteoclastogenesis\u2010associated factors and osteoblast response to osteolytic prostate cancer cells"],"prefix":"10.1002","volume":"70","author":[{"given":"Colm","family":"Morrissey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice S.","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha G.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Chun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine P.","family":"Roudier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilsa M.","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Gulati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Funda","family":"Vakar\u2010Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence D.","family":"True","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Corey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Vessella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,10,28]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.04.140"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1317"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1992.427"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-1382"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-6-71"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)90851-6"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1210"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202332999"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.10.1882"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-15"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2033"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-007-9116-4"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10091"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1809"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.05.003"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.1.101"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.45.183"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01405-4"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200546200"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06368.x"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650090721"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.6.3353"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650110113"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90411-7"}],"container-title":["The 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