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| 001 | 130705 | ||
| 005 | 20240228143455.0 | ||
| 024 | 7 | _ | |a 10.1371/journal.pone.0150507 |2 doi |
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| 037 | _ | _ | |a DKFZ-2017-05783 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Vallet, Sonia |b 0 |
| 245 | _ | _ | |a Pre-Osteoblasts Stimulate Migration of Breast Cancer Cells via the HGF/MET Pathway. |
| 260 | _ | _ | |a Lawrence, Kan. |c 2016 |b PLoS |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1521724225_2108 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The occurrence of skeletal metastases in cancer, e.g. breast cancer (BC), deteriorates patient life expectancy and quality-of-life. Current treatment options against tumor-associated bone disease are limited to anti-resorptive therapies and aimed towards palliation. There remains a lack of therapeutic approaches, which reverse or even prevent the development of bone metastases. Recent studies demonstrate that not only osteoclasts (OCs), but also osteoblasts (OBs) play a central role in the pathogenesis of skeletal metastases, partly by producing hepatocyte growth factor (HGF), which promotes tumor cell migration and seeding into the bone. OBs consist of a heterogeneous cell pool with respect to their maturation stage and function. Recent studies highlight the critical role of pre-OBs in hematopoiesis. Whether the development of bone metastases can be attributed to a particular OB maturation stage is currently unknown.Pre-OBs were generated from healthy donor (HD)-derived bone marrow stromal cells (BMSC) as well as the BMSC line KM105 and defined as ALPlow OPNlow RUNX2high OSX high CD166high. Conditioned media (CM) of pre-OBs, but not of undifferentiated cells or mature OBs, enhanced migration of metastatic BC cells. Importantly, HGF mRNA was significantly up-regulated in pre-OBs versus mature OBs, and CM of pre-OBs activated the MET signaling pathway. Highlighting a key role for HGF, CM from HGF-negative pre-OBs derived from the BMSC line HS27A did not support migration of BC cells. Genetically (siMET) or pharmacologically (INCB28060) targeting MET inhibited both HGF- and pre-OB CM- mediated BC cell migration.Our data demonstrate for the first time a role for pre-OBs in mediating HGF/MET- dependent migration of BC cells and strongly support the clinical evaluation of INCB28060 and other MET inhibitors to limit and/or prevent BC-associated bone metastases. |
| 536 | _ | _ | |a 314 - Tumor immunology (POF3-314) |0 G:(DE-HGF)POF3-314 |c POF3-314 |f POF III |x 0 |
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| 650 | _ | 7 | |a 2-fluoro-N-methyl-4-(7-(quinolin-6-yl-methyl)imidazo(1,2-b)(1,2,4)triazin-2-yl)benzamide |2 NLM Chemicals |
| 650 | _ | 7 | |a Benzamides |2 NLM Chemicals |
| 650 | _ | 7 | |a Bridged Bicyclo Compounds, Heterocyclic |2 NLM Chemicals |
| 650 | _ | 7 | |a Culture Media, Conditioned |2 NLM Chemicals |
| 650 | _ | 7 | |a HGF protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a RNA, Small Interfering |2 NLM Chemicals |
| 650 | _ | 7 | |a Hepatocyte Growth Factor |0 67256-21-7 |2 NLM Chemicals |
| 650 | _ | 7 | |a MET protein, human |0 EC 2.7.10.1 |2 NLM Chemicals |
| 650 | _ | 7 | |a Proto-Oncogene Proteins c-met |0 EC 2.7.10.1 |2 NLM Chemicals |
| 700 | 1 | _ | |a Bashari, Muhammad Hasan |b 1 |
| 700 | 1 | _ | |a Fan, Feng-Juan |b 2 |
| 700 | 1 | _ | |a Malvestiti, Stefano |b 3 |
| 700 | 1 | _ | |a Schneeweiss, Andreas |b 4 |
| 700 | 1 | _ | |a Wuchter, Patrick |b 5 |
| 700 | 1 | _ | |a Jäger, Dirk |0 P:(DE-He78)ed0321409c9cde20b380ae663dbcefd1 |b 6 |u dkfz |
| 700 | 1 | _ | |a Podar, Klaus |0 P:(DE-He78)04fd3ee9c4faa3e73a2271b1e3c37dc0 |b 7 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1371/journal.pone.0150507 |g Vol. 11, no. 3, p. e0150507 - |0 PERI:(DE-600)2267670-3 |n 3 |p e0150507 - |t PLoS one |v 11 |y 2016 |x 1932-6203 |
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