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

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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. Copyright © 2006 American Association for Cancer Research.

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APA

Khalili, P., Arakelian, A., Chen, G., Plunkett, M. L., Beck, I., Parry, G. C., … Rabbani, S. A. (2006). A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo. Molecular Cancer Therapeutics, 5(9), 2271–2280. https://doi.org/10.1158/1535-7163.MCT-06-0100

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