Monitoring of breast cancer progression via aptamer-based detection of circulating tumor cells in clinical blood samples
Year: 2023
Type: article
Abstract: Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX. Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses. Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression. Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.
Authors: Olga S. Kolovskaya, Alena V. Zyuzyukina, Justin P. Dassie, Galina S. Zamay, Tatiana N. Zamay, Nina V. Boyakova, Vladimir A. Khorzhevskii, Daria A. Kirichenko, Ivan N. Lapin, Irina A. Shchugoreva, Polina V. Artyushenko, Felix N. Tomilin, Dmitry V. Veprintsev, Yury E. Glazyrin, Zoran Minic, Vladimir K. Bozhenko, Elena A. Kudinova, Yana Y. Kiseleva, Alexey V. Krat, Eugene V. Slepov, Anton S. Bukatin, Ruslan A. Zukov, Pavel A. Shesternya, Maxim V. Berezovski, Paloma H. Giangrande, Anna S. Kichkailo
Institutions: Russian Academy of Sciences, Krasnoyarsk Scientific Center, Krasnoyarsk State Medical University, Krasnoyarsk Regional Clinical Hospital, University of Iowa, National Research Tomsk State University, Siberian Federal University, Institute of Physics, University of Ottawa, Federal State Budgetary Institution Russian Scientific Center of Roentgenoradiology, Saint Petersburg Academic University, Institute for Analytical Instrumentation, Wave Life Sciences (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4380052559