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

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

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

Authors

Yasunori Tome^{1

2

3}, Hiroaki Kimura^{1

4}, Tasuku Kiyuna^{1

2

3}, Naotoshi Sugimoto⁵, Hiroyuki Tsuchiya⁴, Fuminori Kanaya³, Michael Bouvet², Robert M Hoffman^{1

2}

Affiliations

¹ AntiCancer, Inc., San Diego, CA 92111, USA.
² Department of Surgery, University of California, San Diego, CA 92103, USA.
³ Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan 903-0125.
⁴ Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan 920-8641.
⁵ Department of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan 920-8641.

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.

MeSH terms

Antineoplastic Agents / pharmacology*
Bone Neoplasms / pathology*
Cell Adhesion / drug effects
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Disintegrins / pharmacology
Humans
Integrin alphaVbeta3 / antagonists & inhibitors*
Intercellular Signaling Peptides and Proteins
Neoplasm Invasiveness / pathology
Osteosarcoma / pathology*
Peptides / pharmacology*

Substances

Antineoplastic Agents
Disintegrins
Integrin alphaVbeta3
Intercellular Signaling Peptides and Proteins
Peptides
echistatin