Disintegrin targeting of an &#x03B1; v &#x03B2; 3  integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion  in vitro

Yasunori Tome; Hiroaki Kimura; Tasuku Kiyuna; Naotoshi Sugimoto; Hiroyuki Tsuchiya; Fuminori Kanaya; Michael Bouvet; Robert M. Hoffman

doi:10.18632/oncotarget.10111

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Research Papers:

Disintegrin targeting of an α_vβ₃ integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro

Yasunori Tome, Hiroaki Kimura, Tasuku Kiyuna, Naotoshi Sugimoto, Hiroyuki Tsuchiya, Fuminori Kanaya, Michael Bouvet and Robert M. Hoffman _

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Oncotarget. 2016; 7:46315-46320. https://doi.org/10.18632/oncotarget.10111

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Abstract

Yasunori Tome1,2,3, Hiroaki Kimura1,4, Tasuku Kiyuna1,2,3, Naotoshi Sugimoto5, Hiroyuki Tsuchiya4, Fuminori Kanaya3, Michael Bouvet2, Robert M. Hoffman1,2

1AntiCancer, Inc., San Diego, CA 92111, USA

2Department of Surgery, University of California, San Diego, CA 92103, USA

3Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan 903-0125

4Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan 920-8641

5Department of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan 920-8641

Correspondence to:

Robert M. Hoffman, email: [email protected]

Keywords: α_v β₃ integrin, echistatin, green fluorescent protein/red fluorescent protein, osteosarcoma, metastasis

Received: May 12, 2016 Accepted: June 03, 2016 Published: June 16, 2016

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 α_vβ₃ integrin. Echistatin is an RGD cyclic peptide and an antagonist of α_vβ₃ 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 α_vβ₃ integrin may be an effective target for osteosarcoma.

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

Abstract

Disintegrin targeting of an α_vβ₃ integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro