Key result
Administration of the periostin-targeting DNA aptamer PNDA-3 significantly reduced primary tumor growth and distant metastasis in a 4T1 orthotopic mouse model of breast cancer.
Why the study?
Does PNDA-3 reduce primary tumor growth and distant metastasis in a 4T1 orthotopic mouse model?
Does PNDA-3 reduce primary tumor growth and distant metastasis in a 4T1 orthotopic mouse model?
DNA aptamers targeting periostin (PNDA-3) inhibit breast cancer progression and metastasis in preclinical models, suggesting a potential novel therapeutic approach.
Should not change practice in breast cancer; hypothesis-generating for periostin aptamer development.
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.
No takes yet. Share an insight, caveat, or question.
Lee et al. (2013) studied Breast cancer. PNDA-3 (benzyl-d(U)TP-modified DNA aptamer against human periostin) was evaluated on Primary tumor growth and distant metastasis. Administration of the periostin-targeting DNA aptamer PNDA-3 significantly reduced primary tumor growth and distant metastasis in a 4T1 orthotopic mouse model of breast cancer.
Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context: