Identification of Liver Cancer-Specific Aptamers Using Whole Live Cells

详细信息    查看全文

• 作者：Dihua Shangguan ; Ling Meng ; Zehui Charles Cao ; Zeyu Xiao ; Xiaohong Fang ; Ying Li ; Diana Cardona ; Rafal P. Witek ; Chen Liu ; Weihong Tan
• 刊名：Analytical Chemistry
• 出版年：2008
• 出版时间：February 1, 2008
• 年：2008
• 卷：80
• 期：3
• 页码：721 - 728
• 全文大小：721K
• 年卷期：v.80,no.3(February 1, 2008)
• ISSN：1520-6882

文摘

Liver cancer is the third most deadly cancers in the world.Unfortunately, there is no effective treatment. One of themajor problems is that most cancers are diagnosed in thelater stage, when surgical resection is not feasible. Thus,accurate early diagnosis would significantly improve theclinical outcome of liver cancer. Currently, there are noeffective molecular probes to recognize biomarkers thatare specific for liver cancer. The objective of our currentstudy is to identify liver cancer cell-specific molecularprobes that could be used for liver cancer recognition anddiagnosis. We applied a newly developed cell-SELEX(Systematic Evolution of Ligands by EXponential enrichment) method for the generation of molecular probes forspecific recognition of liver cancer cells. The cell-SELEXuses whole live cells as targets to select aptamers (designed DNA/RNA) for cell recognition. In generatingaptamers for liver cancer recognition, two liver cell lineswere used: a liver cancer cell line BNL 1ME A.7R.1(MEAR) and a noncancer cell line, BNL CL.2 (BNL). Bothcell lines were originally derived from Balb/cJ mice.Through multiple rounds of selection using BNL as acontrol, we have identified a panel of aptamers thatspecifically recognize the cancer cell line MEAR with K_din the nanomolar range. We have also demonstrated thatsome of the selective aptamers could specifically bind livercancer cells in a mouse model. There are two major newresults (compared with our reported cell-SELEX methodology) in addition to the generation of aptamers specifically for liver cancer. The first one is that our currentstudy demonstrates that cell-based aptamer selection canselect specific aptamers for multiple cell lines, even fortwo cell lines with minor differences (MEAR cell is derivedfrom BNL by chemical inducement); and the secondresult is that cell-SELEX can be used for adhesive cellsand thus open the door for solid tumor selection andinvestigation. The newly generated cancer-specific aptamers hold great promise as molecular probes for cancerearly diagnosis and basic mechanism studies.