Toll-Like Receptor-9-Mediated Invasion in Breast Cancer

Abstract

The focus of this research is to discern the structural and biophysical features of small deoxyoligonucleotides that have significant biological properties including the inducement of Toll-like receptor 9 (TLR9) in the mediation of cellular invasion. Cell invasion (metastasis) is a significant problem in the control and treatment of breast cancer. Recent research from our laboratory has demonstrated enhanced cellular invasion in the MDA-MB-231 breast cancer cells by ODN-M362, a 25-base single-stranded CpG-containing deoxyoligonucleotide. Although the mechanism(s) for this induction is unknown, our studies reveal key insights into the structural and sequence requirements for DNA activation of this cellular invasion process. The deoxyoligonucleotides that are most effective in eliciting an invasion response have been shown to adopt stable structural motifs including stem-loops or hairpins or G-quadruplex structures. Sequence modifications have been designed to probe base sequence, structure, and stabilities that are required for initiating TLR-9 mediated cellular invasion. Our results demonstrate that these small deoxyoligonucleotides and the stability of their secondary structures play a pivotal role in eliciting the TLR9-induced invasion process.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2011
Accession Number
ADA549125

Entities

People

  • David E. Graves

Organizations

  • University of Alabama

Tags

DTIC Thesaurus Topics

  • Antineoplastic Agents
  • Biochemistry
  • Breast Cancer
  • Cancer
  • Chemical Synthesis
  • Chemistry
  • Chemotherapy
  • Crystal Structure
  • Deoxyribonucleic Acids
  • Genetics
  • Molecular Biology
  • Molecular Dynamics
  • Neoplasms
  • Organic Chemistry
  • Surface Plasmon Resonance
  • Two Dimensional
  • United States

Fields of Study

  • Biology
  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech