Nucleic Acid Aptamer Selection Against MUC-1 for the Early Diagnosis of Epithelial tumors.

Fall 2010 Proposal for MUC1 Selection

Some of the most prominent carcinomas of the breast, lungs, stomach, pancreas, prostate and ovaries are categorized in a group of epithelial tumors (3). Mucins are glycoproteins that provide a protective layer on epithelial surfaces and are involved in cell-cell interactions, signaling, and metastasis (1). Because

mucins and specifically the MUC1 are such great tum

or markers for epithelial malignancies, they are more readily being used for immunotherapeutic and diagnostic approaches (2). Using aptamer binding techniques to target the specific MUC1 glycoprotein would allow for the formation of new diagnostic assays against the tumor to help with early diagnosis of several types of epithelial malignancies (4).

Figure 1: MUC1 structure

Aptamers are nucleic acid oligonucleotides that bind with specificity and tightness to areas of interest. Developing aptamers against certain targets makes it possible to inhibit the target’s f

unction, consequently reducing the effects of a disease they are linked to (5). Other research has shown that using the SELEX methodology to choose aptamers against MUC1 provided insight to the exact binding site between the aptamer and MUC1 complexes which gives hope to the possibility to improving this detection methodology for further use in early diagnosis techniques (6).

Specific Aim 1:

MUC1 is an excellent epithelial tumor antigen in several different carcinomas around the body. It has been shown that by binding aptamers to MUC1, isolating cancer cells at early stag

es of malignancies can be greatly beneficial to the populace. Thus the selection of RNA aptamers against MUC1 will make cancer cells more apparent at an early stage and destroying those specific cancer cells will become easier.

Figure 2: Mucin acts as an antigen on the surface of most epithelial cancer cells

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References:

1. Ho, J.J.L. "Mucins in the Diagnosis and Therapy of Pancreatic Cancer." Current Pharmaceutical Design 6.18 (2000): 1881-896. Print.
2. Parry, S. "Identification of MUC1 Proteolytic Cleavage Sites in Vivo." Biochemical and Biophysical Research Communications 283.3 (2001): 715-20. Print.
3. Cheng, Alan K. H., Huaipeng Su, Y. Andrew Wang, and Hua-Zhong Yu. "Aptamer-Based Detection of Epithelial Tumor Marker Mucin 1 with Quantum Dot-Based Fluorescence Readout." Analytical Chemistry 81.15 (2009): 6130-139. Print.
4. Ferreira CS, and Papamichael K. "DNA Aptamers against the MUC1 Tumour Marker: Design of Aptamer-antibody Sandwich ELISA for the Early Diagnosis of Epithelial Tumours." Anal Bioanal Chem (2007): 1039-050. Print.
5. Cerchia L, and De Franciscis V. "Targeting Cancer Cells with Nucleic Acid Aptamers." Trends Biotechnol. (2010). Print.
6. Cheng AK,, Su H, Wang YA, and Yu HZ. "Aptamer-based Detection of Epithelial Tumor Marker Mucin 1 with Quantum Dot-based Fluorescence Readout." Anal Chem (2009): 6130-139. Print.