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Antimetastatic potential of PAI-1-specific RNA aptamers.
- Source :
-
Oligonucleotides [Oligonucleotides] 2009 Jun; Vol. 19 (2), pp. 117-28. - Publication Year :
- 2009
-
Abstract
- The serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is increased in several cancers, including breast, where it is associated with a poor outcome. Metastatic breast cancer has a dismal prognosis, as evidenced by treatment goals that are no longer curative but are largely palliative in nature. PAI-1 competes with integrins and the urokinase plasminogen activator receptor on the surface of breast cancer cells for binding to vitronectin. This results in the detachment of tumor cells from the extracellular matrix, which is critical to the metastatic process. For this reason, we sought to isolate RNA aptamers that disrupt the interaction between PAI-1 and vitronectin. Through utilization of combinatorial chemistry techniques, aptamers have been selected that bind to PAI-1 with high affinity and specificity. We identified two aptamers, WT-15 and SM-20, that disrupt the interactions between PAI-1 and heparin, as well as PAI-1 and vitronectin, without affecting the antiprotease activity of PAI-1. Furthermore, SM-20 prevented the detachment of breast cancer cells (MDA-MB-231) from vitronectin in the presence of PAI-1, resulting in an increase in cellular adhesion. Therefore, the PAI-1 aptamer SM-20 demonstrates therapeutic potential as an antimetastatic agent and could possibly be used as an adjuvant to traditional chemotherapy for breast cancer.
- Subjects :
- Aptamers, Nucleotide chemistry
Breast Neoplasms pathology
Cell Adhesion drug effects
Heparin metabolism
Humans
Neoplasm Metastasis
RNA chemistry
SELEX Aptamer Technique
Thrombin metabolism
Aptamers, Nucleotide pharmacology
Breast Neoplasms therapy
Plasminogen Activator Inhibitor 1 metabolism
RNA pharmacology
Vitronectin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1557-8526
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Oligonucleotides
- Publication Type :
- Academic Journal
- Accession number :
- 19284310
- Full Text :
- https://doi.org/10.1089/oli.2008.0177