Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic target.
By: Ghassan M Saed, Nicole M Fletcher, Michael P Diamond, Robert T Morris, Nardhy Gomez-Lopez, Ira Memaj

Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, 275 E Hancock St, Detroit, MI 48201, United States. Electronic address: gsaed@med.wayne.edu.
2017-08-31; doi: 10.1016/j.ygyno.2017.12.018
Abstract

Objective

The objective of this study was to determine the expression, and effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.

Methods

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.

Results

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.

Conclusion

Here we identify CD11b as a novel target, which selectively induces cytotoxicity in ovarian cancer cells.



Copyright © 2017. Published by Elsevier Inc.

PMID:29329880






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