Periostin-binding DNA aptamer inhibits breast cancer growth and metastasis.

Abstract

Periostin is an extracellular matrix (ECM) protein that is overexpressed in a variety of human cancers, and its functions appear to be linked to tumor growth, metastasis, and angiogenesis. Recent clinical evidence suggests that aberrant periostin expression is correlated with poor outcome in patients with breast cancer. To identify novel tools to regulate the functional role of periostin, we generated benzyl-d(U)TP-modified DNA aptamers that were directed against human periostin (PNDAs) and characterized their functional roles in breast cancer progression. PNDA-3 selectively bound to the FAS-1 domain of periostin with nanomolar affinity and disrupted the interaction between periostin and its cell surface receptors, αvβ3 and αvβ5 integrins. PNDA-3 markedly antagonized the periostin-induced adhesion, migration, and invasion of breast cancer cells and blocked the activation of various components of the αvβ3 and αvβ5 integrin signal transduction pathways. In a 4T1 orthotopic mouse model, PNDA-3 administration significantly reduced primary tumor growth and distant metastasis. Thus, our results demonstrated that periostin-integrin signaling regulates breast cancer progression at multiple levels in tumor cells and the tumor microenvironment. DNA aptamers targeting periostin may potentially be used to inhibit breast cancer progression.

• Authors: Yu Jin Lee, Il Shin Kim, Soo-Ah Park, Youndong Kim, Jeung Eun Lee, Dong-Young Noh, Kyong-Tai Kim, Sung Ho Ryu, Pann-Ghill Suh
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 21 Issue 5 Pg. 1004-13 (May 2013) ISSN: 1525-0024 [Electronic] United States
• PMID: 23511245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aptamers, Nucleotide
• Cell Adhesion Molecules
• Integrins
• POSTN protein, human

Topics

• Animals
• Aptamers, Nucleotide (chemistry, genetics, metabolism)
• Base Sequence
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Adhesion (genetics)
• Cell Adhesion Molecules (metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Disease Models, Animal
• Female
• Humans
• Integrins (metabolism)
• Mice
• Molecular Sequence Data
• Neoplasm Metastasis
• Protein Binding
• Signal Transduction
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays