Effect of CD44 Aptamer on Snail Metastasis Factor and Aggressiveness of MDA-MB-231 Breast Cancer Cell Line

The intracellular signaling pathways stimulated by CD44/hyaluronic acid (HA) interaction play a central role in the invasion and migration of cancer cells. Epithelial-mesenchyme transition (EMT) is an important factor in cancer metastasis and migration, which can be stimulated by the snail transcription factor. Previous studies showed cells that were subjected to snailinduced EMT, characterized by a CD44high/CD24low phenotype, expressed at their surface.

The aim of this study was to assess the inhibitory effect of CD44/HA interaction on the snail expression and invasive behavior of aggressive breast cancer cell line with a high CD44 expression in 2D and 3D culture. The cell surface binding capacity of the selected aptamer was evaluated via flow cytometry assay.

To test our hypothesis, we disrupted the CD44/HA interaction by DNA aptamer, which specifically binds to the Hyaluronic Acid Binding Domain (HABD) of CD44. Then, expression level of snail mRNA was evaluated in MDA-MB 231 cells, cultured in 2D and 3D conditions by real-time PCR. Furthermore, invasive behavior was evaluated, using wound healing assay.

The results of this study showed that CD44 aptamer reduced snail expression and invasive behavior in MDA-MB 231 cell line. In addition, our result indicated that cells cultured in 3D were more sensitive to the aptamer in comparison to those cultured in the 2D model.

The inhibition of CD44-HA interaction, using aptamer, negatively regulates the CD44 function in aggressive breast cancer cell line with the high level of CD44 expression.