Nucleic Aptamer Selection Against S100A4 for Prevention of Cancer Metastasis

The full proposal has been posted on Dropbox.

S100A4 (also known as calvasculin) belongs to the S100 family of Ca2+-binding proteins. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. Calvasculin is a polypeptide of 100 amino acids, excluding the initiating N-terminal methionine. The molecular mass of the natural protein, determined by electrospray ionisation mass spectrometry, is 11,646 Da. (Barraclough 1998). The protein has many functions, such as induction of angiogenesis, stimulation of neurite outgrowth and protection of cells from proapoptotic stimuli (Hua et al. 2009). S100A4 may also function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and overexpression of this protein have been implicated in the motility and metastasis of cancer through interactions with cytoskeletal constituents.

S100A4 signaling can focus on factors associated with normal and abnormal proliferation, apoptosis and growth, and differentiation. Therefore, it is arguably a molecular target of considerable potential possessing a wide ranging biological activity that can alter and regulate the major phenotypic features of cancer (Sherbet 2008). RNA ligands, called aptamers act as a promising means to inhibit S100A4. Aptamers bind with high specificity and high affinity to their protein targets and are powerful tools in diagnostics and therapeutics (Stoltenburg et al. 2008). Aptamers against S100A4 are expected to provide a major defense against metastasis of cancer and tumor cells.
Specific Aim 1: Selection of RNA aptamers against S100A4
S100A4 promotes cell progression through angiogenesis and allows tumor neovascularization and cell progression of cancer cells (Sherbet 2008). Therefore decreased levels of this protein correlate to decreased metastasis. Selection of RNA aptamers against S100A4 will decrease metastasis of cancer and tumor cells and since S100A4 also protects from apoptotic stimuli may also induce apoptosis in these malignant cells.

Barraclough, R. 1998. Calcium-binding protein S100A4 in health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1448(2): 190-199.
Hua J., D. Chen, H. Fu, R. Zhang, W. Shen, S. Liu, K. Sun, and X. Sun. 2009. Short hairpin RNA–mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Letters, 292 (1): 41-47.
Sherbet, G.V. 2008. Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy. Cancer Letters, 280(1): 15-30.
Stoltenburg, R., C. Reinemann, and B. Strehlitz. SELEX--a (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomolecular Engineering 24 (4): 381-403.