Invasion of Tumorigenic HT1080 Cells Is Impeded by Blocking or Downregulating the 37-kDa/67-kDa Laminin Receptor
| Autor: | Karin Hoffmann, Vera Mick, Stefan Knackmuss, Melvyn Little, Georg J. Arnold, Daphne Nikles, Harald Lahm, Eckhard Wolf, Thomas Fröhlich, Bertram Brenig, Ekaterina Vlasova, Georgeta Zemora, Daniela Diehl, Chantal Zuber, Uwe Reusch, Stefan Weiss |
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| Rok vydání: | 2008 |
| Předmět: |
PrPSc Proteins
Cell Down-Regulation Biology Receptors Laminin Mice 03 medical and health sciences 0302 clinical medicine Structural Biology Cell Adhesion Tumor Cells Cultured medicine Animals Humans Neoplasm Invasiveness RNA Messenger RNA Small Interfering Cell adhesion Receptor Molecular Biology 030304 developmental biology 0303 health sciences HEK 293 cells Transfection Molecular biology 67 kDa Laminin Receptor medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis NIH 3T3 Cells lipids (amino acids peptides and proteins) HT1080 Laminin Plasmids |
| Zdroj: | Journal of Molecular Biology. 378:530-539 |
| ISSN: | 0022-2836 |
| DOI: | 10.1016/j.jmb.2008.02.004 |
| Popis: | The 37-kDa/67-kDa laminin receptor precursor/laminin receptor (LRP/LR) acting as a receptor for prions and viruses is overexpressed in various cancer cell lines, and their metastatic potential correlates with LRP/LR levels. We analyzed the tumorigenic fibrosarcoma cell line HT1080 regarding 37-kDa/67-kDa LRP/LR levels and its invasive potential. Compared to the less invasive embryonic fibroblast cell line NIH3T3, the tumorigenic HT1080 cells display approximately 1.6-fold higher cell-surface levels of LRP/LR. We show that anti-LRP/LR tools interfere with the invasive potential of HT1080 cells. Anti-LRP/LR single-chain variable fragment antibody (scFv) iS18 generated by chain shuffling from parental scFv S18 and its full-length version immunoglobulin G1-iS18 reduced the invasive potential of HT1080 cells significantly by 37% and 38%, respectively. HT1080 cells transfected with lentiviral plasmids expressing small interfering RNAs directed against LRP mRNA showed reduced LRP levels by approximately 44%, concomitant with a significant decrease in the invasive potential by approximately 37%. The polysulfated glycans HM2602 and pentosan polysulfate (SP-54), both capable of blocking LRP/LR, reduced the invasive potential by 20% and 35%, respectively. Adhesion of HT1080 cells to laminin-1 was significantly impeded by scFv iS18 and immunoglobulin G1-iS18 by 60% and 68%, respectively, and by SP-54 and HM2602 by 80%, suggesting that the reduced invasive capacity achieved by these tools is due to the perturbation of the LRP/LR-laminin interaction on the cell surface. Our in vitro data suggest that reagents directed against LRP/LR or LRP mRNA such as antibodies, polysulfated glycans, or small interfering RNAs, previously shown to encompass an anti-prion activity by blocking or downregulating the prion receptor LRP/LR, might also be potential cancer therapeutics blocking metastasis by interfering with the LRP/LR-laminin interaction in neoplastic tissues. |
| Databáze: | OpenAIRE |
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