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

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...

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Main Authors: Min Jung Kim, Jong Rip Choi, Nara Tae, Tae Min Wi, Kristine M. Kim, Dae Hee Kim, Eung Suk Lee
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/9/3258
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spelling doaj-bd9139f211c545ee8eb33b4d4b79b15e2020-11-25T02:02:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-01213258325810.3390/ijms21093258Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer CellsMin Jung Kim0Jong Rip Choi1Nara Tae2Tae Min Wi3Kristine M. Kim4Dae Hee Kim5Eung Suk Lee6Scripps Korea Antibody Institute, KNU CHUNCHEON CAMPUS, Chuncheon, Gangwon 200-701, KoreaScripps Korea Antibody Institute, KNU CHUNCHEON CAMPUS, Chuncheon, Gangwon 200-701, KoreaScripps Korea Antibody Institute, KNU CHUNCHEON CAMPUS, Chuncheon, Gangwon 200-701, KoreaScripps Korea Antibody Institute, KNU CHUNCHEON CAMPUS, Chuncheon, Gangwon 200-701, KoreaDepartment of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 200-701, KoreaScripps Korea Antibody Institute, KNU CHUNCHEON CAMPUS, Chuncheon, Gangwon 200-701, KoreaScripps Korea Antibody Institute, KNU CHUNCHEON CAMPUS, Chuncheon, Gangwon 200-701, KoreaMucin1 (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.https://www.mdpi.com/1422-0067/21/9/3258MUC1-CMucin1-C terminal domainMetastasissurvivalTNBC
collection DOAJ
language English
format Article
sources DOAJ
author Min Jung Kim
Jong Rip Choi
Nara Tae
Tae Min Wi
Kristine M. Kim
Dae Hee Kim
Eung Suk Lee
spellingShingle Min Jung Kim
Jong Rip Choi
Nara Tae
Tae Min Wi
Kristine M. Kim
Dae Hee Kim
Eung Suk Lee
Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells
International Journal of Molecular Sciences
MUC1-C
Mucin1-C terminal domain
Metastasis
survival
TNBC
author_facet Min Jung Kim
Jong Rip Choi
Nara Tae
Tae Min Wi
Kristine M. Kim
Dae Hee Kim
Eung Suk Lee
author_sort Min Jung Kim
title Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells
title_short Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells
title_full Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells
title_fullStr Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells
title_full_unstemmed Novel Antibodies Targeting MUC1-C Showed Anti-Metastasis and Growth-Inhibitory Effects on Human Breast Cancer Cells
title_sort novel antibodies targeting muc1-c showed anti-metastasis and growth-inhibitory effects on human breast cancer cells
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-05-01
description 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.
topic MUC1-C
Mucin1-C terminal domain
Metastasis
survival
TNBC
url https://www.mdpi.com/1422-0067/21/9/3258
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