{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T03:41:00Z","timestamp":1655782860645},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"2_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Abstract #2052<\/jats:p>\n               <jats:p>Background: Cancer-induced bone destruction is associated with increased osteoclastogenic activity induced by tumor cells, and an unbalanced bone remodelling cycle that favours bone osteolysis. In this proccess the RANK-RANKL signaling is crucial for both osteoclastogenesis and osteoclastic activity. Furthermore, breast cancer cells have been shown to also express the RANK receptor and to increase migration towards RANKL stimuli, however it is not known if RANK - RANKL interaction stimulates breast cancer cell to invade and degrade bone collagen. Objective: To determine if RANKL increases the ability of breast cancer cells to invade a type I collagen matrix and degrade bone collagen. Material and Methods: The influence of sRANKL on MDA-MB-231-BO2 cell migration or cell invasion (type I collagen) were assessed by Boyden-chamber chemotaxis assay. Binding of RANKL to BO2 cells, levels of RANK expression and levels of matrix metalloproteinases secreted during invasion were determined by RT-PCR and WB analysis. The activation of AKT signaling pathway was determined by WB against the phosphorylated form pAKT1\/2\/3(Ser473). Results: sRANKL influences the migration and invasion of RANK-expressing BO2 cells in a dose-dependent manner (dose range 0.75-2.5 ug\/mL), while the neutralization of sRANKL with a specific antibody abrogated this effect. sRANKL stimuli activates AKT pathway downstream of RANK, while the pre-treatment of cells with 100 nM of wortmannin (a PI(3)K inhibitor) blocked this effect and impaired invasion. During invasion of type I collagen the levels MMP1 expression and of secreted MMP1 increase and are positively correlated with the increase in sRANKL concentration. Conclusions: Our data suggest that RANKL can trigger an increase in expression of MMP1 by breast cancer cells expressing RANK, contributing to invasion via degradation of matrix proteins directly by the cancer cells.<\/jats:p>\n               <jats:p>Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2052.<\/jats:p>","DOI":"10.1158\/0008-5472.sabcs-2052","type":"journal-article","created":{"date-parts":[[2010,12,30]],"date-time":"2010-12-30T23:31:29Z","timestamp":1293751889000},"page":"2052","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RANKL plays a role in migration and invasion of the bone-seeking cell line MDA-MB-231-BO2 through human type I collagen by up-regulating MMP1."],"prefix":"10.1158","volume":"69","author":[{"given":"S","family":"Casimiro","sequence":"first","affiliation":[{"name":"1 Unidade de Investigacao Aplicada em Oncologia Clinica, Hospital de Santa Maria & Instituto de Medicina Molecular, Lisbon, Portugal"}]},{"given":"I","family":"Alho","sequence":"additional","affiliation":[{"name":"1 Unidade de Investigacao Aplicada em Oncologia Clinica, Hospital de Santa Maria & Instituto de Medicina Molecular, Lisbon, Portugal"}]},{"given":"A","family":"Fernandes","sequence":"additional","affiliation":[{"name":"1 Unidade de Investigacao Aplicada em Oncologia Clinica, Hospital de Santa Maria & Instituto de Medicina Molecular, Lisbon, Portugal"}]},{"given":"A","family":"Lipton","sequence":"additional","affiliation":[{"name":"2 Hershey Medical Centre, Hershey, PA"}]},{"given":"T","family":"Guise","sequence":"additional","affiliation":[{"name":"3 Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA"}]},{"given":"L","family":"Costa","sequence":"additional","affiliation":[{"name":"1 Unidade de Investigacao Aplicada em Oncologia Clinica, Hospital de Santa Maria & Instituto de Medicina Molecular, Lisbon, Portugal"}]}],"member":"1086","container-title":["Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/69\/2_Supplement\/2052\/551880\/RANKL-plays-a-role-in-migration-and-invasion-of","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/69\/2_Supplement\/2052\/551880\/RANKL-plays-a-role-in-migration-and-invasion-of","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T03:03:53Z","timestamp":1655780633000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/69\/2_Supplement\/2052\/551880\/RANKL-plays-a-role-in-migration-and-invasion-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":0,"journal-issue":{"issue":"2_Supplement","published-print":{"date-parts":[[2009,1,15]]}},"URL":"https:\/\/doi.org\/10.1158\/0008-5472.sabcs-2052","relation":{},"ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2009,1]]},"published":{"date-parts":[[2009,1]]}}}