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Int. J. Mol. Sci. 2018, 19(7), 2004; https://doi.org/10.3390/ijms19072004

A Novel Monoclonal Antibody Targets Mucin1 and Attenuates Growth in Pancreatic Cancer Model

1
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Korea
2
Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Korea
3
Peptron, Inc., 37-24, Yuseong-daero 1628 beon gil, Daejeon 34054, Korea
4
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 16 May 2018 / Revised: 26 June 2018 / Accepted: 4 July 2018 / Published: 9 July 2018
(This article belongs to the Special Issue Cell and Molecular Biology of Pancreatic Disorders)
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Abstract

Mucin1 (MUC1) is a highly glycosylated transmembrane protein that plays a crucial role in the lubrication and protection of normal epithelial cells. However, MUC1 has emerged as a potential target for cancer therapy because it is overexpressed and functions in several types of cancers. Recently, we produced a monoclonal antibody (the anti-hMUC1 antibody) specific to the extracellular region of the MUC1 subunit MUC1-C to evaluate the utility of using anti-MUC1 antibodies in pancreatic cancer models. The anti-hMUC1 antibody recognized the MUC1-C protein in pancreatic cancer cells. Based on immunostaining and confocal image analyses, the anti-hMUC1 antibody initially bound to the cell membrane then was internalized in cancer cells that express MUC1. The anti-hMUC1 antibody suppressed epidermal growth factor (EGF)-mediated extracellular signal–regulated kinase (ERK) phosphorylation and cyclin D1 expression. When the anti-hMUC1 antibody was injected into a xenograft mouse model and traced using an in vivo imaging system, we observed that the anti-hMUC1 antibody was localized to MUC1-expressing pancreatic tumors. Importantly, the anti-hMUC1 monoclonal antibody suppressed pancreatic tumor growth in mice. According to immunohistochemistry analysis using a pancreatic cancer tissue array and the anti-hMUC1 antibody, MUC1 was highly expressed in human pancreatic cancer tissues compared to normal tissues. Therefore, we conclude that the anti-hMUC1 antibody specifically targets MUC1 and suppresses its function in pancreatic cancer in vitro and in vivo and can be further developed as a promising targeted therapy to treat pancreatic cancer. View Full-Text
Keywords: Mucin1; monoclonal antibody; pancreatic cancer; antibody therapeutics; targeting Mucin1; monoclonal antibody; pancreatic cancer; antibody therapeutics; targeting
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wu, G.; Maharjan, S.; Kim, D.; Kim, J.N.; Park, B.K.; Koh, H.; Moon, K.; Lee, Y.; Kwon, H.-J. A Novel Monoclonal Antibody Targets Mucin1 and Attenuates Growth in Pancreatic Cancer Model. Int. J. Mol. Sci. 2018, 19, 2004.

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