Anti-tumor effect of the anti-KL-6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping

Cancer Science
Mihoko DoiNobuoki Kohno

Abstract

Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein that is frequently overexpressed on the surface of many human adenocarcinomas. Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor-associated antigen that has been intensely studied as a target for cancer immunotherapy. We previously identified a mouse IgG(1) mAb that recognizes a sialylated sugar chain, designated as KL-6, classified in 'Cluster 9 (MUC1)'. Using the anti-KL-6 mAb, we investigated antitumor effects of anti-MUC1 mAb on breast cancer cell lines expressing MUC1 abundantly. We showed that anti-KL-6 mAb induced capping of MUC1 and facilitated E-cadherin-mediated cell-cell interaction in the breast cancer cell lines YMB-S and ZR-75-1S, which proliferate in suspension culture without aggregation. Moreover, anti-KL-6 mAb enhanced the cytotoxic activity of lymphokine-activated killer cells. These results indicate that the capping of MUC1 restores cell surface proteins, such as adhesion molecules and tumor antigens, to work in cell-cell interactions, leading to inhibition of tumor proliferation due to cell-cell adhesion and increased accessibility to effector cells that are needed to kill tumor cells.

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Citations

Mar 1, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·G J Mizejewski
Jan 3, 2007·Biochemical and Biophysical Research Communications·Hiroyasu ShodaNobuoki Kohno
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Sonosuke TanakaNobuoki Kohno
May 5, 2012·Respiratory Investigation·Nobuhisa IshikawaNobuoki Kohno
Apr 14, 2017·BMC Cancer·Yasushi HorimasuNobuoki Kohno
Oct 7, 2020·Immunotherapy·Mona PourjafarMassoud Saidijam
Jun 3, 2009·Cancer Research·John Maher, Scott Wilkie

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