Anti-tumor effect of the anti-KL-6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping.
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| 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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| Authors | Mihoko Doi, Akihito Yokoyama, Keiichi Kondo, Hiroshi Ohnishi, Nobuhisa Ishikawa, Noboru Hattori, Nobuoki Kohno |
| Journal | Cancer science (Cancer Sci) Vol. 97 Issue 5 Pg. 420-9 (May 2006) ISSN: 1347-9032 [Print] England |
| PMID | 16630141 (Publication Type: Journal Article) |
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