Publikationer från Malmö universitet
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Sialic Acid as a Biomarker Studied in Breast Cancer Cell Lines In Vitro Using Fluorescent Molecularly Imprinted Polymers
Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.ORCID-id: 0000-0002-0841-5804
Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
Lund University.
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2021 (Engelska)Ingår i: Applied Sciences, E-ISSN 2076-3417, Vol. 11, nr 7, artikel-id 3256Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Sialylations are post-translational modifications of proteins and lipids that play important roles in many cellular events, including cell-cell interactions, proliferation, and migration. Tumor cells express high levels of sialic acid (SA), which are often associated with the increased invasive potential in clinical tumors, correlating with poor prognosis. To overcome the lack of natural SA-receptors, such as antibodies and lectins with high enough specificity and sensitivity, we have used molecularly imprinted polymers (MIPs), or "plastic antibodies", as nanoprobes. Because high expression of epithelial cell adhesion molecule (EpCAM) in primary tumors is often associated with proliferation and a more aggressive phenotype, the expression of EpCAM and CD44 was initially analyzed. The SA-MIPs were used for the detection of SA on the cell surface of breast cancer cells. Lectins that specifically bind to the a-2,3 SA and a-2,6 SA variants were used for analysis of SA expression, with both flow cytometry and confocal microscopy. Here we show a correlation of EpCAM and SA expression when using the SA-MIPs for detection of SA. We also demonstrate the binding pattern of the SA-MIPs on the breast cancer cell lines using confocal microscopy. Pre-incubation of the SA-MIPs with SA-derivatives as inhibitors could reduce the binding of the SA-MIPs to the tumor cells, indicating the specificity of the SA-MIPs. In conclusion, the SA-MIPs may be a new powerful tool in the diagnostic analysis of breast cancer cells.

Ort, förlag, år, upplaga, sidor
MDPI, 2021. Vol. 11, nr 7, artikel-id 3256
Nyckelord [en]
breast cancer, epithelial cell adhesion molecule, molecularly imprinted polymers, nanoparticles, sialic acid
Nationell ämneskategori
Analytisk kemi
Identifikatorer
URN: urn:nbn:se:mau:diva-42033DOI: 10.3390/app11073256ISI: 000638354600001Scopus ID: 2-s2.0-85104259855OAI: oai:DiVA.org:mau-42033DiVA, id: diva2:1548095
Tillgänglig från: 2021-04-29 Skapad: 2021-04-29 Senast uppdaterad: 2024-02-05Bibliografiskt granskad
Ingår i avhandling
1. Glycosylation in cancer and infection: the role of sialic acid
Öppna denna publikation i ny flik eller fönster >>Glycosylation in cancer and infection: the role of sialic acid
2021 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Sialic acids (SA), a group of nine-carbon backbone monosaccharides are abundantly expressed in vertebrates. They are usually linked to the terminal of glycan chains and play crucial roles in many biological processes, including cell adhesion, cell-cell interactions, immune modulation, cancer cell migration and invasion, as well as viral infections. To analyze and monitor SA expression, antibodies and glycan-binding lectins are typically used. However, high costs and poor stability limit the application in SA analysis. To overcome these drawbacks, an imprinting technique was used to synthesize an alternative SA receptor – SA molecularly imprinted polymers (SA-MIPs). Fluorescent molecules are embedded into the MIPs, facilitating the detection of MIPs binding to cells by flow cytometry and fluorescence microscopy. Firstly, core-shell SA imprinted MIPs were used to analyze SA expression in a panel of breast cancer cell lines. The SA expression of these cell lines was also tested by using the two glycan-binding lectins, MAL andSNA, which recognize α2,3 and α2,6 SA, respectively. Our results show that breast cancer cell lines express α2,3 and α2,6 SA dissimilarly, and hence present different SA-MIP binding patterns. The specificity of SA-MIPs was further verified by an inhibition assay using two pentavalent SA conjugates that interfere with the SAMIPs.Furthermore, the SA-MIP synthesis protocol has been improved by using silica-coated polystyrene particles. The polystyrene core particles are lighter and smaller, increasing MIP suspensibility and augmenting MIP-cancer cell interactions. The cancer cell binding properties and the specificity have been verified by using thirteen different cancer cell lines, showing that the SA-MIPs can be used as effective tools for SA expression analysis. The SA-MIPs were used to analyze the SA expression of in vitro cultured cells treated with soluble cytokines to mimic the tumor microenvironment. The SA expression of two cancer cell lines stimulated with soluble cytokines was analyzed by using lectins and SA-MIPs. The MIPbinding data correlated well with lectin staining results, demonstrating the potential of SA-MIPs to be used in the analysis of overexpressed SA in the tumor microenvironment. Furthermore, the involvement of SA in the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed. The viral surface receptor-binding domain (RBD) recognizes and conjugates with receptors on host cells, triggering the infection. Although the interaction between the RBD and host cells has been extensively studied, the mechanism behind this reaction is not fully determined. In this study, the interaction between the viral RBD and a panel of human cell lines from tissues susceptible to viral infection was tested. Moreover, the role of SA in this interaction has also been tested and evaluated.

Ort, förlag, år, upplaga, sidor
Malmo: Malmö universitet, 2021. s. 58
Serie
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 2021:7
Nyckelord
Cancer, sialic acids, receptor, molecularly imprinted polymers, SARS-CoV-2, fluorescence
Nationell ämneskategori
Biomaterialvetenskap Cellbiologi
Forskningsämne
Hälsa och samhälle
Identifikatorer
urn:nbn:se:mau:diva-46316 (URN)10.24834/isbn.9789178772216 (DOI)978-91-7877-220-9 (ISBN)978-91-7877-221-6 (ISBN)
Disputation
2021-11-05, HS assembly hall, JAN WALDENSTRÖMS GATA 25, Malmo, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2021-10-14 Skapad: 2021-10-14 Senast uppdaterad: 2022-08-16Bibliografiskt granskad

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El-Schich, ZahraZhang, YuechengPersson, Jenny L.Shinde, SudhirkumarSellergren, BörjeGjörloff Wingren, Anette

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El-Schich, ZahraZhang, YuechengPersson, Jenny L.Shinde, SudhirkumarSellergren, BörjeGjörloff Wingren, Anette
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Institutionen för biomedicinsk vetenskap (BMV)Biofilms Research Center for Biointerfaces
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