Disintegrin targeting of an αvβ3 integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro
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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
Robert M. Hoffman, email: email@example.com
Keywords: αv β3 integrin, echistatin, green fluorescent protein/red fluorescent protein, osteosarcoma, metastasis
Received: May 12, 2016 Accepted: June 03, 2016 Published: June 16, 2016
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.
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