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,Fuminori Kanaya,Hiroyuki Tsuchiya,Michael Bouvet,Robert M Hoffman,Hiroaki Kimura,Naotoshi Sugimoto,Tasuku Kiyuna

doi:10.18632/oncotarget.10111

Yasunori Tome, Fuminori Kanaya + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.10111

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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.

Highlights

Osteosarcoma is the most common bone cancer in children and adolescents [1,2,3]
To determine whether echistatin inhibited 143BLM4 cell proliferation, 143B-LM4 cells were treated with echistatin at various concentrations. 143B-LM4 cell proliferation decreased after treatment with echistatin in a time-dependent and a dose-dependent manner (P
After 24 hr treatment, 143B-LM4 cell proliferation was decreased to 44.0% at 0.5 μg/mL; 34.8% at 1.0 μg/mL echistatin; and 28.1% at 5.0 μg/mL echistatin, compared to control (P

Summary

Introduction

Osteosarcoma is the most common bone cancer in children and adolescents [1,2,3]. Osteosarcoma usually arises in the distal femur and proximal tibia and proximal humerus.Development of neo-adjuvant chemotherapy has increased the rate of overall survival and has enabled surgery, but the failure rate is still high, causing death in children and adolescents [4,5,6,7].Novel more effective targets for osteosarcoma therapy are needed. Αvβ3 integrin-over-expressing high-metastatic variants of the human osteosarcoma cell line 143B were previously isolated and termed 143B-LM4. Over-expression of αvβ3 integrin in the variant selected for high-metastasis suggested that integrin maybe a promising target for osteosarcoma.

Results

Conclusion