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

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Cancer metastasis is a leading cause of cancer-related deaths globally.
• Intercellular adhesion molecule-1 (ICAM-1) on cancer cells facilitates tumor cell attachment, invasion, and migration.
• Targeting ICAM-1 offers a potential strategy to inhibit cancer metastasis.

Purpose of the Study:

• To generate and characterize DNA aptamers that specifically bind to ICAM-1.
• To evaluate the potential of these aptamers in detecting ICAM-1-expressing cancer cells.
• To assess the ability of aptamers to inhibit cancer cell migration and invasion.

Main Methods:

• DNA aptamers were generated against ICAM-1 using cell-SELEX and protein SELEX methods.
• Sequencing and characterization of enriched aptamer sequences for binding affinity (K_d) to ICAM-1⁽⁺⁾ and ICAM-1^(-) cells.
• In vitro assessment of aptamer-mediated inhibition of cancer cell migration and invasion.

Main Results:

• Seven aptamer sequences were identified with selective binding to ICAM-1⁽⁺⁾ CHO-ICAM-1 cells, exhibiting K_d values between 13.8 and 47.1 nM.
• Four of these aptamers demonstrated significant inhibition (≥61%) of both migration and invasion in CHO-ICAM-1 cells.
• The selected aptamers showed specific binding to ICAM-1 expressing cells, distinguishing them from ICAM-1^(-) cells.

Conclusions:

• The generated DNA aptamers show high specificity and affinity for ICAM-1.
• These aptamers hold promise for the specific detection of ICAM-1-expressing tumor cells.
• The aptamers' ability to inhibit cell migration and invasion suggests potential therapeutic applications in blocking ICAM-1-mediated metastasis.