Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells
| Autor: | Shuichiro Maeda, Atsushi Sasaki, Kenichi Amagasaki, Hideaki Nukui, Goro Kato, Hirofumi Naganuma |
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| Rok vydání: | 2001 |
| Předmět: |
endocrine system
Cancer Research DNA Complementary Angiogenesis Blotting Western Genetic Vectors Motility Biology Transfection Thrombospondin 1 Gentamicin protection assay Cell Movement Glioma Sense (molecular biology) Cell Adhesion Tumor Cells Cultured medicine Humans Dose-Response Relationship Drug virus diseases Oligonucleotides Antisense medicine.disease Molecular biology Oncology Cancer cell Immunology Peptides Protein Binding |
| Zdroj: | International Journal of Cancer. 94:508-512 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-β. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisense-transfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a dose-related manner. Maximum inhibition of migration was achieved by 100 μg/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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