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Open AccessArticle

Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells

1
Scripps Korea Antibody Institute, KNU Chuncheon Campus, Chuncheon, Gangwon 200-701, Korea
2
Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 200-701, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(9), 3258; https://doi.org/10.3390/ijms21093258
Received: 6 April 2020 / Revised: 26 April 2020 / Accepted: 29 April 2020 / Published: 5 May 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Mucin1 (MUC1) is aberrantly glycosylated and overexpressed in various cancers, and it plays a crucial role in cancerogenesis. MUC1 is a type I membranous protein composed of α and β subunits. MUC1-α can be cleaved in cancers, exposing MUC1-β (MUC1-C). MUC1-C is involved with multiple cancer cellular functions, which makes it an attractive target for cancer treatment. However, its multifunctional mechanisms have not been fully elucidated and there has not been a successful therapeutic development against MUC1-C. Through a phage display process, we isolated the specific antibodies for the extracellular domain of MUC1-C. The relevant full IgG antibodies were produced successfully from mammalian cells and validated for their MUC1-C specificities through ELISA, dual FACS analysis, BLI assay, and confocal image analysis. In the comparison with reference antibody, elected antibodies showed characteristic bindings on target antigens. In the functionality assessment of high-ranking antibodies, SKM1-02, -13, and -20 antibodies highly inhibited invasion by triple-negative breast cancer (TNBC) cells and the SKM1-02 showed strong growth inhibition of cancer cells. Our results showed that these MUC1-C specific antibodies will be important tools for the understanding of MUC1 oncogenesis and are also highly effective therapeutic candidates against human breast cancers, especially TNBC cells. View Full-Text
Keywords: MUC1-C; Mucin1-C terminal domain; Metastasis; survival; TNBC MUC1-C; Mucin1-C terminal domain; Metastasis; survival; TNBC
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MDPI and ACS Style

Kim, M.J.; Choi, J.R.; Tae, N.; Wi, T.M.; Kim, K.M.; Kim, D.H.; Lee, E.S. Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells. Int. J. Mol. Sci. 2020, 21, 3258.

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