論文 - 詳細
| RRC ID | 11945 |
|---|---|
| 著者 | Lavazza C, Carlo-Stella C, Giacomini A, Cleris L, Righi M, Sia D, Di Nicola M, Magni M, Longoni P, Milanesi M, Francolini M, Gloghini A, Carbone A, Formelli F, Gianni AM. |
| タイトル | Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature. |
| ジャーナル | Blood |
| Abstract |
Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction. |
| 巻・号 | 115(11) |
| ページ | 2231-40 |
| 公開日 | 2010-3-18 |
| DOI | 10.1182/blood-2009-08-239632 |
| PII | S0006-4971(20)56633-0 |
| PMID | 20075160 |
| MeSH | Animals Antigens, CD34 / metabolism* Apoptosis Blood Vessels / metabolism Blood Vessels / pathology Cell Line, Tumor Cell Membrane / metabolism* Cell Transplantation Chemokine CXCL12 / metabolism Genetic Engineering* Hemorrhage / pathology Humans Mice Necrosis Neoplasms / blood supply* Neoplasms / genetics Neoplasms / pathology Neoplasms / therapy* Neovascularization, Pathologic / pathology Neovascularization, Pathologic / therapy Protein Binding TNF-Related Apoptosis-Inducing Ligand / metabolism* Tissue Distribution Vascular Cell Adhesion Molecule-1 / metabolism Xenograft Model Antitumor Assays |
| IF | 17.794 |
| 引用数 | 28 |
| WOS 分野 | HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | hTRAIL/pMKITneo human TRAIL cDNA (RDB02934) |