title: 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.affiliation: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Il Shin
authors.initials: IS
authors.lastname: Kim
authors.forename: Soo-Ah
authors.initials: SA
authors.lastname: Park
authors.forename: Youndong
authors.initials: Y
authors.lastname: Kim
authors.forename: Jeung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011485:Protein Binding; D015398:Signal Transduction; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; D016023:Integrins; C512835:POSTN protein, human