Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic target
•CD11b is unexpectedly expressed in ovarian cancer cells and tissues.•Targeting CD11b with its antibody kills ovarian cancer cells, in vitro and in vivo.•CD11b antibody did not kill normal ovarian surface epithelial cells nor macrophages.•CD11b antibody exhibited a synergistic effect with traditiona...
Gespeichert in:
Veröffentlicht in: | Gynecologic oncology 2018-03, Vol.148 (3), p.567-575 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | •CD11b is unexpectedly expressed in ovarian cancer cells and tissues.•Targeting CD11b with its antibody kills ovarian cancer cells, in vitro and in vivo.•CD11b antibody did not kill normal ovarian surface epithelial cells nor macrophages.•CD11b antibody exhibited a synergistic effect with traditional chemotherapeutic drugs.•Cytoxicity of the CD11b antibody is mediated through a mechanism involving myeloperoxidase.
The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.
CD11b expression was determined in epithelial ovarian cancer (EOC) cell lines and tissues by immunofluorescence and flow cytometry. Cytotoxicity of the CD11b antibody and synergism with chemothearapeutic drugs were determined by the MTT Cell Proliferation Assay in human macrophages, normal ovarian epithelial cells, and in both sensitive and chemoresistant EOC cell lines. Cell migration was assessed with a scratch assay and in vivo effects of the CD11b antibody was assessed with a nude mouse ovarian cancer xenograft model. Data was analyzed with either t-tests or one-way ANOVA.
CD11b was unexpectedly expressed in several EOC lines and tissues, but not normal tissues. Targeting CD11b with its monoclonal antibody resulted in intriguing cytotoxic effects in sensitive and chemoresistant EOC lines, while surprisingly not affecting normal cells. More importantly, the cytotoxicity of the CD11b antibody when combined with chemotherapeutic drugs (cisplatin or docetaxel) was significantly synergistic, in both sensitive and chemoresistant EOC cells. The anti-tumorigenic effect of the CD11b antibody was confirmed in an ovarian cancer nude mouse xenograft model.
Here we identify CD11b as a novel target, which selectively induces cytotoxicity in ovarian cancer cells. |
---|---|
ISSN: | 0090-8258 1095-6859 |
DOI: | 10.1016/j.ygyno.2017.12.018 |