Novel Aptamers to Target Metastasis
Annual rept. 1 Sep 2010-31 Aug 2011
MICHIGAN UNIV ANN ARBOR
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Metastasis and tumor progression at metastatic sites ultimately results in the demise of prostate cancer PCa patients. currently there are no highly effective methods that can target these problems. Aptamers, which have proven clinical efficacy for non-neoplastic disease and are generally more specific and stable than antibodies, may have clinical utility in PCa. However, defining apatamers that can prevent metastasis is challenging due to the fact that many proteins that play a role in the metastatic process are unknown. The overall goal of this project is to develop novel method to inhibit cancer metastasis. The Major hypothesis to be tested is that aptamers short oligonucleotides can be developed that target the process of invasion, without prior knowledge of a target protein, and that these aptamers will inhibit the development of metastasis. We also hypothesize that the aptamers can be used to identify cell surface proteins that are important mediators of metastasis. This latter information is important as it may help identify further therapeutic targets. We have made some initial progress towards testing this hypothesis. Specifically, we have identified aptamers, using a novel application of a process called systemic evolution of ligands by exponential enrichment SELEX reviewed in Brody, 10680, that bind PCa cells that we selected for their high metastatic ability. We now propose to test these aptamers for their ability to inhibit metastasis and identify their target protein.
- Medicine and Medical Research