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Theranostics 2018; 8(1):78-91. doi:10.7150/thno.21278 This issue Cite

Research Paper

A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer

Guang Wu1*, Dongbum Kim1*, Jung Nam Kim2, Sangkyu Park3, Sony Maharjan1, Heeju Koh4, Kyungduk Moon4, Younghee Lee3✉, Hyung-Joo Kwon1, 2✉

1. Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
2. Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
3. Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea
4. Peptron, Inc., 37-24, Yuseong-daero 1628 beon gil, Daejeon 34054, Republic of Korea
*Equal contribution to this work

✉ Corresponding authors: Kwon HJ, Tel: +82 (33) 248-2635; Fax: +82 (33) 241-3640; E‑mail: hjookwonac.kr. Lee Y, +82 (43) 261-3387; Fax: +82 (43) 267-2306; e-mail: yhl4177ac.kr.

Citation:
Wu G, Kim D, Kim JN, Park S, Maharjan S, Koh H, Moon K, Lee Y, Kwon HJ. A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer. Theranostics 2018; 8(1):78-91. doi:10.7150/thno.21278. https://www.thno.org/v08p0078.htm
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Abstract

Graphic abstract

Background: Mucin1 (MUC1) is a highly glycosylated transmembrane protein that has gained attention because of its overexpression in various cancers. However, MUC1-targeted therapeutic antibodies have not yet been approved for cancer therapy. MUC1 is cleaved to two subunits, MUC1-N and MCU1-C. MUC1-N is released from the cell surface, making MUC1-C a more reasonable target for cancer therapy. Therefore, we produced a monoclonal antibody (anti-hMUC1) specific to the extracellular region of MUC1-C and evaluated its effects in vitro and in vivo.

Methods: We produced a monoclonal antibody (anti-hMUC1) using a purified recombinant human MUC1 polypeptide and our novel immunization protocol. The reactivity of anti-hMUC1 was characterized by ELISA, western blotting and immunoprecipitation analyses. The localization of the antibody in the breast cancer cells after binding was determined by confocal image analysis. The effects of the antibody on the growth of cells were also investigated. We injected anti-hMUC1 and performed in vivo tracing analysis in xenograft mouse models. In addition, expression of MUC1 in tissue sections from patients with breast cancer was assessed by immunohistochemistry with anti-hMUC1.

Results: The anti-hMUC1 antibody recognized recombinant MUC1 as well as native MUC1-C protein in breast cancer cells. Anti-hMUC1 binds to the membrane surface of cells that express MUC1 and is internalized in some cancer cell lines. Treatment with anti-hMUC1 significantly reduced proliferation of cells in which anti-hMUC1 antibody is internalized. Furthermore, the anti-hMUC1 antibody was specifically localized in the MUC1-expressing breast cancer cell-derived tumors in xenograft mouse models. Based on immunohistochemistry analysis, we detected significantly higher expression of MUC1 in cancer tissues than in normal control tissues. Conclusion: Our results reveal that the anti-hMUC1 antibody targets the extracellular region of MUC1-C subunit and may have utility in future applications as an anti-breast cancer agent.

Keywords: Mucin1, monoclonal antibody, breast cancer, antibody therapeutics, targeting

Citation styles

APA
Wu, G., Kim, D., Kim, J.N., Park, S., Maharjan, S., Koh, H., Moon, K., Lee, Y., Kwon, H.J. (2018). A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer. Theranostics, 8(1), 78-91. https://doi.org/10.7150/thno.21278.

ACS
Wu, G.; Kim, D.; Kim, J.N.; Park, S.; Maharjan, S.; Koh, H.; Moon, K.; Lee, Y.; Kwon, H.J. A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer. Theranostics 2018, 8 (1), 78-91. DOI: 10.7150/thno.21278.

NLM
Wu G, Kim D, Kim JN, Park S, Maharjan S, Koh H, Moon K, Lee Y, Kwon HJ. A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer. Theranostics 2018; 8(1):78-91. doi:10.7150/thno.21278. https://www.thno.org/v08p0078.htm

CSE
Wu G, Kim D, Kim JN, Park S, Maharjan S, Koh H, Moon K, Lee Y, Kwon HJ. 2018. A Mucin1 C-terminal Subunit-directed Monoclonal Antibody Targets Overexpressed Mucin1 in Breast Cancer. Theranostics. 8(1):78-91.

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