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Cancers 2019, 11(3), 356; https://doi.org/10.3390/cancers11030356

Size Matters: The Functional Role of the CEACAM1 Isoform Signature and Its Impact for NK Cell-Mediated Killing in Melanoma

1
Skin Cancer Unit of the Dermatology Department, Medical Faculty, University Duisburg-Essen, West German Cancer Center, Essen 45147, Germany
2
German Cancer Consortium (DKTK) partner site Düsseldorf/Essen, Essen 45147, Germany
3
Institute of Anatomy, Medical Faculty, University Duisburg-Essen, Essen 45147, Germany
*
Author to whom correspondence should be addressed.
Received: 3 December 2018 / Revised: 21 February 2019 / Accepted: 9 March 2019 / Published: 13 March 2019
(This article belongs to the Special Issue Natural Killer Cells and Cancer Therapy)
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Abstract

Malignant melanoma is the most aggressive and treatment resistant type of skin cancer. It is characterized by continuously rising incidence and high mortality rate due to its high metastatic potential. Various types of cell adhesion molecules have been implicated in tumor progression in melanoma. One of these, the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is a multi-functional receptor protein potentially expressed in epithelia, endothelia, and leukocytes. CEACAM1 often appears in four isoforms differing in the length of their extracellular and intracellular domains. Both the CEACAM1 expression in general, and the ratio of the expressed CEACAM1 splice variants appear very dynamic. They depend on both the cell activation stage and the cell growth phase. Interestingly, normal melanocytes are negative for CEACAM1, while melanomas often show high expression. As a cell–cell communication molecule, CEACAM1 mediates the direct interaction between tumor and immune cells. In the tumor cell this interaction leads to functional inhibitions, and indirectly to decreased cancer cell immunogenicity by down-regulation of ligands of the NKG2D receptor. On natural killer (NK) cells it inhibits NKG2D-mediated cytolysis and signaling. This review focuses on novel mechanistic insights into CEACAM1 isoforms for NK cell-mediated immune escape mechanisms in melanoma, and their clinical relevance in patients suffering from malignant melanoma. View Full-Text
Keywords: CEACAM1; NKG2D ligands; melanoma; NK cells CEACAM1; NKG2D ligands; melanoma; NK cells
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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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Helfrich, I.; Singer, B.B. Size Matters: The Functional Role of the CEACAM1 Isoform Signature and Its Impact for NK Cell-Mediated Killing in Melanoma. Cancers 2019, 11, 356.

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