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

Mol Cancer Ther. 2006 Sep;5(9):2271-80. doi: 10.1158/1535-7163.MCT-06-0100.


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 alpha5beta1 and alphavbeta3 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Bone Neoplasms / prevention & control*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Female
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / drug therapy
  • Oligopeptides / pharmacology*
  • Radiography / instrumentation
  • Soft Tissue Neoplasms / prevention & control
  • Soft Tissue Neoplasms / secondary
  • Transfection
  • Xenograft Model Antitumor Assays


  • Oligopeptides
  • Green Fluorescent Proteins
  • acetyl-prolyl-histidyl-seryl-cysteinyl-asparaginamide