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...
Main Authors: | , , , , , , |
---|---|
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 |
id |
doaj-bd9139f211c545ee8eb33b4d4b79b15e |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT minjungkim novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells AT jongripchoi novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells AT naratae novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells AT taeminwi novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells AT kristinemkim novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells AT daeheekim novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells AT eungsuklee novelantibodiestargetingmuc1cshowedantimetastasisandgrowthinhibitoryeffectsonhumanbreastcancercells |
_version_ |
1724951942712524800 |