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. 2016 Jul 19;7(29):46315-46320.
doi: 10.18632/oncotarget.10111.

Disintegrin targeting of an αvβ3 integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro

Yasunori Tome  1   2   3 , Hiroaki Kimura  1   4 , Tasuku Kiyuna  1   2   3 , Naotoshi Sugimoto  5 , Hiroyuki Tsuchiya  4 , Fuminori Kanaya  3 , Michael Bouvet  2 , Robert M Hoffman  1   2
Affiliations

Disintegrin targeting of an αvβ3 integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro

Yasunori Tome et al. Oncotarget. .

Abstract

The in vitro efficacy of the disintegrin echistatin was tested on a high-metastatic variant of 143B human osteosarcoma, 143B-LM4, which over-expresses αvβ3 integrin. Echistatin is an RGD cyclic peptide and an antagonist of αvβ3 integrin. In the present study, echistatin inhibited cell proliferation, migration, invasion, and adhesion of 143B-LM4 cells. 143B-LM4 cell proliferation decreased after treatment with echistatin in a time-dependent and dose-dependent manner (P <0.01). In vitro migration and invasion of 143B-LM4 cells were also inhibited by echistatin in a dose-dependent manner (P <0.01, respectively). Cell adhesion to vitronectin of 143B-LM4 cells was also inhibited by echistatin in a dose-dependent manner (P <0.01). These results suggest that αvβ3 integrin may be an effective target for osteosarcoma.

Keywords: echistatin; green fluorescent protein/red fluorescent protein; metastasis; osteosarcoma; αv β3 integrin.

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Conflict of interest statement

No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1. Dual-color selected 143B-LM4 human osteosarcoma cells expressing GFP in the nucleus and RFP in the cytoplasm in vitro
Images were obtained with a Fluoview FV1000 laser-scanning confocal microscope (Olympus Corp., Tokyo, Japan). GFP was excited at 488 nm, RFP at 543nm. Magnification 60x. Scale bar: 50 μm.
Figure 2
Figure 2. Echistatin decreased proliferation of 143B-LM4 cells in vitro
A. Efficacy of echistatin on 143B-LM4 cell proliferation. Proliferation of 143B-LM4 cells was inhibited by echistatin and decreased in a time-dependent and a dose-dependent manner (P <0.01). Error bars: SEM. B. visualization of the efficacy of echistatin at various concentrations on 143B-LM4 cell proliferation at 72 hours. Cell number decreased in a dose-dependent manner. Images were obtained with the Olympus IX71 fluorescence microscope. Magnification, 20×.
Figure 3
Figure 3. Echistatin decreased migration and invasion of 143B-LM4 cells in vitro
A. Efficacy of echistatin on 143B-LM4 cell migration in vitro. 143B-LM4 cells were seeded into the upper compartment of transwell chambers (Corning® HTS Transwell-96 uncoated plates, (Tewksbury, MA). Migration of 143B-LM4 cells decreased in a dose-dependent manner (P <0.01). Error bars: SEM. B. Efficacy of echistatin on 143B-LM4 invasion in vitro. 143B-LM4 cells were seeded into the upper compartment of transwell chambers with the surface coated with a basement membrane extract. Invasion of 143B-LM4 cells decreased in a dose-dependent manner (P <0.01). Error bars: SEM. Absorbance was evaluated with a plate reader after cells which migrated or invaded were treated with MTS.
Figure 4
Figure 4. Echistatin decreased adhesion to vitronectin of 143B-LM4 cells in vitro
Efficacy of echistatin on 143B-LM4 cell adhesion to Vitronectin (Trevigen, Gaithersburg, MD) in vitro (Corning® HTS Transwell-96 plates (Tewksbury, MA) coated with Vitronectin. Adhesion of 143B-LM4 cells decreased in a dose-dependent manner (P <0.01). Error bars: SEM. Absorbance was evaluated with a plate reader after adherent cells were treated with MTS.
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References

    1. Hong WK, Bast RC, Jr, Hait WN, Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E., III . Holland-Frei Cancer Medicine. 8. People's Medical Publishing House; Shelton, CT: 2010.
    1. Huvos AG. Osteogenic sarcoma. In: Huvos AG, editor. Bone Tumors: Diagnosis, Treatment and Prognosis. Second. Philadelphia: WB Saunders; 1991. pp. 85–155.
    1. Unni KK. Osteosarcoma. In: Unni KK, Inwards CY, editors. Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases. Fifth. New York: Lippincott-Raven; 1996. pp. 143–183.
    1. Tsuchiya H, Tomita K, Mori Y, Asada N, Morinaga T, Kitano S, Yamamoto N. Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic osteosarcoma. Anticancer Res. 1998;18:657–666. - PubMed
    1. Bacci G, Picci P, Ferrari S, Ruggieri P, Casadei R, Tienghi A, Brach del Prever A, Gherlinzoni F, Mercuri M, Monti C. Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer. 1993;72:3227–3238. - PubMed

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