| pubmed-article:20106902 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20106902 | lifeskim:mentions | umls-concept:C0024109 | lld:lifeskim |
| pubmed-article:20106902 | lifeskim:mentions | umls-concept:C0079633 | lld:lifeskim |
| pubmed-article:20106902 | lifeskim:mentions | umls-concept:C0031670 | lld:lifeskim |
| pubmed-article:20106902 | lifeskim:mentions | umls-concept:C0205217 | lld:lifeskim |
| pubmed-article:20106902 | lifeskim:mentions | umls-concept:C0086982 | lld:lifeskim |
| pubmed-article:20106902 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:20106902 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:20106902 | pubmed:dateCreated | 2010-3-31 | lld:pubmed |
| pubmed-article:20106902 | pubmed:abstractText | Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. This study analyzed the soluble factors secreted by lung cancer cells, which are responsible for increasing osteoclast differentiation. Addition of recombinant human interleukin-8 (rhIL-8), present in large amounts in A549-conditioned medium (CM) and NCI-H460-CM, mimicked the inductive effect of A549-CM and NCI-H460-CM on osteoclastogenesis. In contrast, depletion of interleukin-8 (IL-8) from A549-CM and NCI-H460-CM decreased the osteoclastogenesis-inductive properties of A549-CM and NCI-H460-CM. Induction of osteoclast differentiation by lung cancer-derived-CM and rhIL-8 was associated with increased phospholipase D (PLD) activation, and the activations of protein kinase C (PKC) alpha/betaII, extracellular signal-regulated kinase (ERK) 1/2 and AKT/the mammalian target of rapamycin (mTOR). Blocking PLD by a specific inhibitor significantly decreased osteoclast formation by inhibiting PKCs activation and subsequently attenuating the phosphorylation of ERK1/2. PLD inhibitor also completely decreased AKT and mTOR phosphorylation, whereas phosphatidylinositol-3-kinase (PI3K) inhibitor only partially decreased mTOR phosphorylation, suggesting that mTOR activation by PLD is through both PI3K/AKT-dependent and PI3K/AKT-independent manner. In addition, blocking AKT and ERK1/2 by a specific inhibitor also suppressed lung cancer-derived-CM and rhIL-8-induced osteoclast differentiation. Moreover, treatment of peripheral blood mononuclear cells with sera from invasive lung cancer patients increased the formation of osteoclasts. Our study suggests that IL-8 or IL-8-mediated PLD/PKC/ERK1/2 or PLD/AKT signaling is an attractive therapeutic target for osteolytic bone metastases in lung cancer patients. | lld:pubmed |
| pubmed-article:20106902 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20106902 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20106902 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20106902 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:20106902 | pubmed:issn | 1460-2180 | lld:pubmed |
| pubmed-article:20106902 | pubmed:author | pubmed-author:KoYing-ChinYC | lld:pubmed |
| pubmed-article:20106902 | pubmed:author | pubmed-author:HungJen-YuJY | lld:pubmed |
| pubmed-article:20106902 | pubmed:author | pubmed-author:HuangMing-Shy... | lld:pubmed |
| pubmed-article:20106902 | pubmed:author | pubmed-author:KuoPo-LinPL | lld:pubmed |
| pubmed-article:20106902 | pubmed:author | pubmed-author:HungChih-Hsin... | lld:pubmed |
| pubmed-article:20106902 | pubmed:author | pubmed-author:HsuYa-LingYL | lld:pubmed |
| pubmed-article:20106902 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20106902 | pubmed:volume | 31 | lld:pubmed |
| pubmed-article:20106902 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20106902 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20106902 | pubmed:pagination | 587-96 | lld:pubmed |
| pubmed-article:20106902 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
| pubmed-article:20106902 | pubmed:meshHeading | pubmed-meshheading:20106902... | lld:pubmed |
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| pubmed-article:20106902 | pubmed:meshHeading | pubmed-meshheading:20106902... | lld:pubmed |
| pubmed-article:20106902 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20106902 | pubmed:articleTitle | Phospholipase D signaling pathway is involved in lung cancer-derived IL-8 increased osteoclastogenesis. | lld:pubmed |
| pubmed-article:20106902 | pubmed:affiliation | Graduate Institute of Medicine, Schoolof Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. | lld:pubmed |
| pubmed-article:20106902 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20106902 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:3576 | entrezgene:pubmed | pubmed-article:20106902 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:20106902 | lld:entrezgene |
