| pubmed-article:20826454 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C0330390 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C0016030 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C0033414 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C1416912 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C1524075 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C1517050 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C0072034 | lld:lifeskim |
| pubmed-article:20826454 | lifeskim:mentions | umls-concept:C0337112 | lld:lifeskim |
| pubmed-article:20826454 | pubmed:issue | Pt 19 | lld:pubmed |
| pubmed-article:20826454 | pubmed:dateCreated | 2010-9-16 | lld:pubmed |
| pubmed-article:20826454 | pubmed:abstractText | Interactions between cancer cells and fibroblasts are crucial in cancer progression. We have previously shown that the aspartic protease cathepsin D (cath-D), a marker of poor prognosis in breast cancer that is overexpressed and highly secreted by breast cancer cells, triggers mouse embryonic fibroblast outgrowth via a paracrine loop. Here, we show the requirement of secreted cath-D for human mammary fibroblast outgrowth using a three-dimensional co-culture assay with breast cancer cells that do or do not secrete pro-cath-D. Interestingly, proteolytically-inactive pro-cath-D remains mitogenic, indicating a mechanism involving protein-protein interaction. We identify the low-density lipoprotein (LDL) receptor-related protein-1, LRP1, as a novel binding partner for pro-cath-D in fibroblasts. Pro-cath-D binds to residues 349-394 of the ? chain of LRP1, and is the first ligand of the extracellular domain of LRP1? to be identified. We show that pro-cath-D interacts with LRP1? in cellulo. Interaction occurs at the cell surface, and overexpressed LRP1? directs pro-cath-D to the lipid rafts. Our results reveal that the ability of secreted pro-cath-D to promote human mammary fibroblast outgrowth depends on LRP1 expression, suggesting that pro-cath-D-LRP1? interaction plays a functional role in the outgrowth of fibroblasts. Overall, our findings strongly suggest that pro-cath-D secreted by epithelial cancer cells promotes fibroblast outgrowth in a paracrine LRP1-dependent manner in the breast tumor microenvironment. | lld:pubmed |
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| pubmed-article:20826454 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20826454 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20826454 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:20826454 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20826454 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:20826454 | pubmed:issn | 1477-9137 | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:HymanBradley... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:Hollingsworth... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:van der... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:SmithGary KGK | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:PattingreSoph... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:YaoZeminZ | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:Laurent-Matha... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:ZhangHongyuH | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:Liaudet-Coopm... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:DerocqDaniell... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:PréboisChrist... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:BettacheNadir... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:BeaujouinMéla... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:CoopmanPeterP | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:MassonOlivier... | lld:pubmed |
| pubmed-article:20826454 | pubmed:author | pubmed-author:GrossfieldJam... | lld:pubmed |
| pubmed-article:20826454 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20826454 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:20826454 | pubmed:volume | 123 | lld:pubmed |
