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      Ulex Europaeus Agglutinin-I-Based Magnetic Isolation for the Efficient and Specific Capture of SW480 Circulating Colorectal Tumor Cells

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          Abstract

          The efficient and specific capture of circulating tumor cells (CTCs) from patients’ peripheral blood is of significant value in precise cancer diagnosis and cancer therapy. As fine targeting molecules, lectins can recognize cancer cells specifically due to the abnormal glycosylation of molecules on the cancer cell membrane and the specific binding of lectin with glycoconjugates. Herein, a Ulex europaeus agglutinin-I (UEA-I)-based magnetic isolation strategy was developed to efficiently and specifically capture α-1,2-fucose overexpression CTCs from colorectal cancer (CRC) patients’ peripheral blood. Using UEA-I-modified Fe 3O 4 magnetic beads (termed MB-UEA-I), up to 94 and 89% of target cells (i.e., SW480 CRC cells) were captured from the cell spiking complete cell culture medium and whole blood, respectively. More than 90% of captured cells show good viability and proliferation ability without detaching from MB-UEA-I. In combination with three-color immunocytochemistry (ICC) identification, MB-UEA-I has been successfully used to capture CTCs from CRC patients’ peripheral blood. The experimental results indicate a correlation between CTC characterization and tumor metastasis. Specifically, MB-UEA-I can be applied to screen early CRC by capturing CTCs when served as a liquid biopsy. The presented work offers a new insight into developing cost-effective lectin-functionalized methods for biomedical applications.

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          A perspective on cancer cell metastasis.

          Metastasis causes most cancer deaths, yet this process remains one of the most enigmatic aspects of the disease. Building on new mechanistic insights emerging from recent research, we offer our perspective on the metastatic process and reflect on possible paths of future exploration. We suggest that metastasis can be portrayed as a two-phase process: The first phase involves the physical translocation of a cancer cell to a distant organ, whereas the second encompasses the ability of the cancer cell to develop into a metastatic lesion at that distant site. Although much remains to be learned about the second phase, we feel that an understanding of the first phase is now within sight, due in part to a better understanding of how cancer cell behavior can be modified by a cell-biological program called the epithelial-to-mesenchymal transition.
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            Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

            The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
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              Circulating tumor cells, disease progression, and survival in metastatic breast cancer.

              We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers. Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P 18 months, P 18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer. Copyright 2004 Massachusetts Medical Society
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                Author and article information

                Journal
                ACS Omega
                ACS Omega
                ao
                acsodf
                ACS Omega
                American Chemical Society
                2470-1343
                17 August 2022
                30 August 2022
                : 7
                : 34
                : 30405-30411
                Affiliations
                []State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China
                []University of Science and Technology of China , Jinzhai Road, Baohe District, Hefei, Anhui 230026, P. R. China
                [§ ]Department of Radiology, The First Hospital of Jilin University , Changchun, Jilin 130021, P. R. China
                Author notes
                Author information
                https://orcid.org/0000-0001-7451-2058
                https://orcid.org/0000-0002-1908-9848
                Article
                10.1021/acsomega.2c03702
                9435041
                36061664
                ef872c07-5789-4d07-925d-484264bdc255
                © 2022 The Authors. Published by American Chemical Society

                Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 June 2022
                : 08 August 2022
                Funding
                Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
                Award ID: 21974133
                Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;
                Award ID: 81871406
                Categories
                Article
                Custom metadata
                ao2c03702
                ao2c03702

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