Ghassan M Saed1, Nicole M Fletcher2, Michael P Diamond3, Robert T Morris4, Nardhy Gomez-Lopez5, Ira Memaj6. 1. 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. 2. 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: nfletche@med.wayne.edu. 3. Department of Obstetrics and Gynecology, Augusta University, 1120 15th Street, BA-7300, Augusta, GA 30912, United States. Electronic address: michael.diamond@augusta.edu. 4. Karmanos Cancer Center, 4100 John R, Detroit, MI 48201, United States. Electronic address: rmorris@med.wayne.edu. 5. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, United States; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, United States. Electronic address: ngomezlo@med.wayne.edu. 6. 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: ira.memaj@wayne.edu.
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.
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 mouseovarian 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.
Authors: Carolina Rubio; José Avendaño-Ortiz; Raquel Ruiz-Palomares; Viktoriya Karaivanova; Omaira Alberquilla; Rebeca Sánchez-Domínguez; José Carlos Casalvilla-Dueñas; Karla Montalbán-Hernández; Iris Lodewijk; Marta Rodríguez-Izquierdo; Ester Munera-Maravilla; Sandra P Nunes; Cristian Suárez-Cabrera; Miriam Pérez-Crespo; Víctor G Martínez; Lucía Morales; Mercedes Pérez-Escavy; Miguel Alonso-Sánchez; Roberto Lozano-Rodríguez; Francisco J Cueto; Luis A Aguirre; Félix Guerrero-Ramos; Jesús M Paramio; Eduardo López-Collazo; Marta Dueñas Journal: Cancers (Basel) Date: 2022-01-07 Impact factor: 6.639