Anti-KL-6/MUC1 monoclonal antibody reverses resistance to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity by capping MUC1.

Antibodies, Monoclonal / pharmacology Antibody-Dependent Cell Cytotoxicity / drug effects Antineoplastic Agents, Immunological / pharmacology Breast Neoplasms / drug therapy Cell Death / drug effects Cell Line, Tumor Drug Resistance, Neoplasm / drug effects Female Humans Mucin-1 / immunology Signal Transduction / drug effects Trastuzumab / pharmacology
Antibody-dependent cell-mediated cytotoxicity Capping KL-6 MUC1 Trastuzumab

Journal

Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053

Informations de publication

Date de publication:
01 02 2019
Historique:
received: 08 01 2018
revised: 14 10 2018
accepted: 25 10 2018
pubmed: 6 11 2018
medline: 5 11 2019
entrez: 4 11 2018
Statut: ppublish

Résumé

Polymorphic epithelial mucin (MUC1) is generally overexpressed on the surface of most adenocarcinomas including breast cancer. MUC1 is associated with chemotherapeutic resistance and immune evasion of cancer cells; however, the association between MUC1 and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) remains unclear. In this study, using six breast cancer cell lines with differing expression levels and MUC1 distribution, the present results show that cells with MUC1 overexpression and uniform surface distribution were resistant to trastuzumab-mediated ADCC. Importantly, trastuzumab resistance was reversed upon siRNA-mediated MUC1 knockdown and by using anti-KL-6/MUC1 monoclonal antibody (mAb). Additionally, we visually confirmed that anti-KL-6/MUC1 mAb induced capping of MUC1 molecules on the cell surface, resulting the in death of these cells. These results suggest that not only the quantity but also the cell-surface distribution of MUC1 affects the sensitivity of breast cancer cells to trastuzumab-mediated ADCC.

Identifiants

DOI: 10.1016/j.canlet.2018.10.037 PMID: 30389434
pubmed: 30389434
pii: S0304-3835(18)30652-9
doi: 10.1016/j.canlet.2018.10.037
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antineoplastic Agents, Immunological 0
MUC1 protein, human 0
Mucin-1 0
Trastuzumab P188ANX8CK

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

31-39

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.

Auteurs

Masashi Namba (M)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Noboru Hattori (N)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Electronic address: nhattori@hiroshima-u.ac.jp.

Hironobu Hamada (H)

Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Kakuhiro Yamaguchi (K)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Yohei Okamoto (Y)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Taku Nakashima (T)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Takeshi Masuda (T)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Shinjiro Sakamoto (S)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Yasushi Horimasu (Y)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Shintaro Miyamoto (S)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Hiroshi Iwamoto (H)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Kazunori Fujitaka (K)

Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Nobuoki Kohno (N)

Hiroshima Cosmopolitan University, 5-13-18 Ujinanishi, Minami-ku, Hiroshima, 734-0014, Japan.

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Classifications MeSH

Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Phénomènes du système immunitaire › Cytotoxicité immunologique › Cytotoxicité à médiation cellulaire dépendante des anticorps › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Mort cellulaire › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Antigènes glycanniques associés aux tumeurs › Mucine-1 › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Transduction du signal › Anti-KL-6/MUC1 monoclonal antibody reverses...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Trastuzumab › Anti-KL-6/MUC1 monoclonal antibody reverses...