A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo

Parisa Khalili, Ani Arakelian, Gaoping Chen, Marian L. Plunkett, Ivy Beck, Graham C. Parry, Fernando Doñate, David E. Shaw, Andrew P. Mazar, Shafaat A. Rabbani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Purpose: Integrins are expressed by numerous tumor types including breast cancer, in which they play a crucial role in tumor growth and metastasis. In this study, we evaluated the ability of ATN-161 (Ac-PHSCN-NH2), a 5-mer capped peptide derived from the synergy region of fibronectin that binds to α5β 1 and αvβ3 in vitro, to block breast cancer growth and metastasis. Experimental design: MDA-MB-231 human breast cancer cells were inoculated s.c. in the right flank, or cells transfected with green fluorescent protein (MDA-MB-231-GFP) were inoculated into the left ventricle of female BALB/c nu/nu mice, resulting in the development of skeletal metastasis. Animals were treated with vehicle alone or by i.v. infusion with ATN-161 (0.05-1 mg/kg thrice a week) for 10 weeks. Tumor volume was determined at weekly intervals and tumor metastasis was evaluated by X-ray, microcomputed tomography, and histology. Tumors were harvested for histologic evaluation. Result: Treatment with ATN-161 caused a significant dose-dependent decrease in tumor volume and either completely blocked or caused a marked decrease in the incidence and number of skeletal as well as soft tissue metastases. This was confirmed histologically as well as radiographically using X-ray and microcomputed tomography. Treatment with ATN-161 resulted in a significant decrease in the expression of phosphorylated mitogen-activated protein kinase, microvessel density, and cell proliferation in tumors grown in vivo. Conclusion: These studies show that ATN-161 can block breast cancer growth and metastasis, and provides a rationale for the clinical development of ATN-161 for the treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)2271-2280
Number of pages10
JournalMolecular cancer therapeutics
Volume5
Issue number9
DOIs
StatePublished - Sep 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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