{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:50:18Z","timestamp":1785336618579,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,5,9]],"date-time":"2008-05-09T00:00:00Z","timestamp":1210291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["42511"],"award-info":[{"award-number":["42511"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ontario Cancer Research Network","award":["04MAY00089"],"award-info":[{"award-number":["04MAY00089"]}]},{"name":"U.S P.H.S","award":["CA87728"],"award-info":[{"award-number":["CA87728"]}]},{"DOI":"10.13039\/100000182","name":"U.S. Army Medical Research and Materiel Command","doi-asserted-by":"crossref","award":["DAMD17-2-01-0541"],"award-info":[{"award-number":["DAMD17-2-01-0541"]}],"id":[{"id":"10.13039\/100000182","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Breast cancer metastasis suppressor 1 (BRMS1) inhibits the ability of multiple human and murine cancer cell lines to metastasize to lymph nodes, bones and lungs. Comparison of mRNA expression in metastatic MDA\u2010MB\u2010435 human carcinoma cells (435) and metastasis\u2010suppressed BRMS1 transfectants (435\/BRMS1) showed a marked (&gt;90%) reduction of osteopontin (OPN) mRNA and protein expression in BRMS1\u2010overexpressing cells. OPN expression is associated with disease progression in patients, with higher levels of OPN produced by cancer cells associated with poorer patient survival. Furthermore, OPN has been suggested to promote survival of cancer cells in response to stress, although the mechanisms by which this may occur remain poorly understood. This study tested the hypothesis that re\u2010expression of OPN in metastasis\u2010suppressed 435\/BRMS1 cells would reverse metastasis suppression and confer protection from stress\u2010induced apoptosis. A stable pooled population of OPN overexpressing 435\/BRMS1 cells was created (435\/BRMS1\/OPN). OPN re\u2010expression did not affect <jats:italic>in vitro<\/jats:italic> cell growth rates; however, increased anchorage independent growth\/survival and protection from hypoxia\u2010induced apoptosis was observed (<jats:italic>p<\/jats:italic> &lt; 0.05). <jats:italic>In vivo<\/jats:italic>, OPN re\u2010expression in BRMS1 transfected cells did not affect <jats:italic>in vivo<\/jats:italic> primary tumor growth but did increase the incidence of spontaneous metastasis to lymph nodes and lungs in mice. These novel findings suggest that OPN downregulation by BRMS1 may be responsible, at least in part, for BRMS1\u2010mediated metastasis suppression by sensitizing cancer cells to stress induced apoptosis. These studies clarify one mechanism by which BRMS1 can suppress metastasis. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23542","type":"journal-article","created":{"date-parts":[[2008,5,9]],"date-time":"2008-05-09T19:48:00Z","timestamp":1210362480000},"page":"526-534","source":"Crossref","is-referenced-by-count":35,"title":["Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1"],"prefix":"10.1002","volume":"123","author":[{"given":"Benjamin D.","family":"Hedley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny R.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison L.","family":"Allan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Al\u2010Katib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Dales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl O.","family":"Postenka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Casey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"MacDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann F.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.57.1.43"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1672"},{"key":"e_1_2_6_4_2","volume-title":"Principles and practice of oncology","author":"DeVita VH","year":"2005"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/ctrv.2000.0207"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890101)63:1<181::AID-CNCR2820630129>3.0.CO;2-H"},{"key":"e_1_2_6_7_2","first-page":"244","article-title":"Prognostic factors in breast cancer","volume":"19","author":"Elledge RM","year":"1992","journal-title":"Semin Oncol"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67887-7"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66544-0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05483-6"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000051580.89109.4b"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/80.3.200"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr87"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.21.1717"},{"key":"e_1_2_6_15_2","first-page":"8866","article-title":"Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1","volume":"61","author":"Hunter KW","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1569"},{"key":"e_1_2_6_17_2","first-page":"2764","article-title":"Functional evidence for a novel human breast carcinoma metastasis suppressor. BRMS1, encoded at chromosome 11q13","volume":"60","author":"Seraj MJ","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5452"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022542519586"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3139"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-6-6"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.713.65.3"},{"key":"e_1_2_6_23_2","first-page":"1765","article-title":"Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication","volume":"61","author":"Saunders MM","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307969200"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1405-2"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601839"},{"key":"e_1_2_6_27_2","first-page":"605","article-title":"Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival","volume":"3","author":"Singhal H","year":"1997","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2354"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014734930781"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19981023)79:5<502::AID-IJC10>3.0.CO;2-3"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20105"},{"key":"e_1_2_6_32_2","first-page":"1235","article-title":"Decreased levels of osteopontin and bone sialoprotein II are correlated with reduced proliferation, colony formation, and migration of GFP\u2010MDA\u2010MB\u2010231 cells","volume":"24","author":"Adwan H","year":"2004","journal-title":"Int J Oncol"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051152"},{"key":"e_1_2_6_34_2","first-page":"810","article-title":"Beta(3) integrin expression increases breast carcinoma cell responsiveness to the malignancy\u2010enhancing effects of osteopontin","volume":"1","author":"Furger KA","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407952200"},{"key":"e_1_2_6_36_2","first-page":"717","article-title":"Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice","volume":"50","author":"Price JE","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-006-9392-8"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-004-3759-1"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90191-V"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013095329825"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602694200"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.01.010"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1570013"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-005-0745-1"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0635"},{"key":"e_1_2_6_46_2","first-page":"2541","article-title":"Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency","volume":"60","author":"Cameron MD","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10170"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210096"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22320"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12980"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10039"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1347"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1159\/000086955"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1055-3207(18)30406-X"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1055-3207(18)30198-4"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji111"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.23542","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.23542","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.23542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T17:15:36Z","timestamp":1697476536000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.23542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,28]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1002\/ijc.23542"],"URL":"https:\/\/doi.org\/10.1002\/ijc.23542","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,28]]}}}