Inhibition of cell migration and invasion by ICAM-1 binding DNA aptamers

Abstract

Cancer is the second leading cause of death worldwide and most of the cancer-related deaths result from metastasis. As expressed on the surface of various cancer cell types, intercellular adhesion molecule-1 (ICAM-1) has been shown to play a role in the attachment, invasion and migration of tumor cells. In this study, DNA aptamers were generated against ICAM-1 by cell-SELEX and protein SELEX method using ICAM-1⁽⁺⁾ CHO-ICAM-1 cells and ICAM-1 protein, respectively. The pools obtained at the end of the 10th round of both SELEX were sequenced and the most enriched sequences were characterized for their binding behaviors and affinities to ICAM-1⁽⁺⁾ CHO-ICAM-1 and ICAM-1^(-) MIA PaCa-2 cells. Moreover, the inhibition abilities of sequences on migration and invasion were measured. The seven aptamer sequences were obtained selectively binding to CHO-ICAM-1 cells with K_d values in the ranging from 13.8 to 47.1 nM. Four of these aptamers showed inhibition in both migration and invasion of CHO-ICAM-1 cells at least 61%. All these results suggested that these aptamers have potential to detect specifically ICAM-1 expressing tumor cells and inhibit migration and invasion by blocking ICAM-1 related interactions of circulating tumor cells.

Keywords: Aptamer; Cancer; ICAM-1; Invasion; Migration; SELEX.